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Vinay Pathak | University of Mumbai - Academia.edu
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id="ProfileCheckPaperUpdate-react-component-2cb1a940-c8a1-45b5-a59c-0da114b58178"></div> <div class="DesignSystem"><div class="onsite-ping" id="onsite-ping"></div></div><div class="profile-user-info DesignSystem"><div class="social-profile-container"><div class="left-panel-container"><div class="user-info-component-wrapper"><div class="user-summary-cta-container"><div class="user-summary-container"><div class="social-profile-avatar-container"><img class="profile-avatar u-positionAbsolute" border="0" alt="" src="//a.academia-assets.com/images/s200_no_pic.png" /></div><div class="title-container"><h1 class="ds2-5-heading-sans-serif-sm">Vinay Pathak</h1><div class="affiliations-container fake-truncate js-profile-affiliations"><div><a class="u-tcGrayDarker" href="https://mu.academia.edu/">University of Mumbai</a>, <a class="u-tcGrayDarker" href="https://mu.academia.edu/Departments/Ty_BMS/Documents">Ty BMS</a>, <span class="u-tcGrayDarker">Undergraduate</span></div></div></div></div><div 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100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Vinay Pathak</h3></div><div class="js-work-strip profile--work_container" data-work-id="122873305"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873305/Survey_of_int_Region_DNA_Rearrangements_in_C3H_and_BALB_cfC3H_Mouse_Mammary_Tumor_System23"><img alt="Research paper thumbnail of Survey of int Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System23" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873305/Survey_of_int_Region_DNA_Rearrangements_in_C3H_and_BALB_cfC3H_Mouse_Mammary_Tumor_System23">Survey of int Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System23</a></div><div class="wp-workCard_item"><span>JNCI: Journal of the National Cancer Institute</span><span>, 1987</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BAL...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BALB/cfC3H hyperplastic alveolar nodule and its hyperplastic outgrowth (HPO) model systems by examining the DNA of the different stages of the neoplastic progression, with use of the Southern blot technique. Rearrangement of int region DNAs associated with proviral amplification occurred more frequently in spontaneous tumors (19 of 27) than in tumors from HPOs (7 of 37) and rarely occurred in HPOs (1 of 29). However, the int-1 rearrangement maintained in 1 BALB/cfC3H HPO line through 11 transplant generations suggests that the int-1 rearrangement is neither sufficient nor necessary for progression to mouse mammary carcinoma.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873305"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873305"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873305; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873305]").text(description); $(".js-view-count[data-work-id=122873305]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873305; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873305']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873305, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873305]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873305,"title":"Survey of int Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System23","translated_title":"","metadata":{"abstract":"Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BALB/cfC3H hyperplastic alveolar nodule and its hyperplastic outgrowth (HPO) model systems by examining the DNA of the different stages of the neoplastic progression, with use of the Southern blot technique. 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We constructed spleen necrosis virus (SNV)-based viral vectors that contained large direct repeats flanking the viral encapsidation sequence (E). A large proportion of the proviruses in the target cells had E and one copy of the direct repeat deleted. Direct repeats of 1,333 and 788 bp were deleted at frequencies of 93 and 85%, respectively. To achieve a 100% deletion efficiency in target cells after ex vivo infection and drug selection, we constructed a self-activating vector that simultaneously deleted E and reconstituted the neomycin phosphotransferase gene. Selection of the target cells for resistance to G418 (a neomycin analog) ensured that all integrated proviruses had E deleted. The proviruses with E deleted were mobilized by a replication-competent virus 267,000-fold less efficiently than proviruses with E. We named thes...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873304"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873304"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873304; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873304]").text(description); $(".js-view-count[data-work-id=122873304]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873304; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873304']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873304, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873304]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873304,"title":"E- vectors: development of novel self-inactivating and self-activating retroviral vectors for safer gene therapy","translated_title":"","metadata":{"abstract":"We have developed novel self-inactivating and self-activating retroviral vectors based on the previously observed high-frequency deletion of direct repeats. 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We named thes...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1995,"errors":{}},"publication_name":"Journal of virology"},"translated_abstract":"We have developed novel self-inactivating and self-activating retroviral vectors based on the previously observed high-frequency deletion of direct repeats. We constructed spleen necrosis virus (SNV)-based viral vectors that contained large direct repeats flanking the viral encapsidation sequence (E). A large proportion of the proviruses in the target cells had E and one copy of the direct repeat deleted. Direct repeats of 1,333 and 788 bp were deleted at frequencies of 93 and 85%, respectively. To achieve a 100% deletion efficiency in target cells after ex vivo infection and drug selection, we constructed a self-activating vector that simultaneously deleted E and reconstituted the neomycin phosphotransferase gene. Selection of the target cells for resistance to G418 (a neomycin analog) ensured that all integrated proviruses had E deleted. The proviruses with E deleted were mobilized by a replication-competent virus 267,000-fold less efficiently than proviruses with E. We named thes...","internal_url":"https://www.academia.edu/122873304/E_vectors_development_of_novel_self_inactivating_and_self_activating_retroviral_vectors_for_safer_gene_therapy","translated_internal_url":"","created_at":"2024-08-14T06:25:58.584-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"E_vectors_development_of_novel_self_inactivating_and_self_activating_retroviral_vectors_for_safer_gene_therapy","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":49161,"name":"Safety","url":"https://www.academia.edu/Documents/in/Safety"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":181936,"name":"Gene","url":"https://www.academia.edu/Documents/in/Gene"},{"id":295728,"name":"Molecular cloning","url":"https://www.academia.edu/Documents/in/Molecular_cloning"},{"id":620070,"name":"Transfection","url":"https://www.academia.edu/Documents/in/Transfection"},{"id":990417,"name":"Recombinant Proteins","url":"https://www.academia.edu/Documents/in/Recombinant_Proteins"},{"id":2894265,"name":"Restriction Mapping","url":"https://www.academia.edu/Documents/in/Restriction_Mapping"},{"id":2940274,"name":"virus integration","url":"https://www.academia.edu/Documents/in/virus_integration"},{"id":3061075,"name":"Genetic Therapy","url":"https://www.academia.edu/Documents/in/Genetic_Therapy"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873303"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873303/The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate"><img alt="Research paper thumbnail of The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873303/The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate">The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1997</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3&#39;-azido-3&#39;-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873303"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873303"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873303; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873303]").text(description); $(".js-view-count[data-work-id=122873303]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873303; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873303']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873303, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873303]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873303,"title":"The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate","translated_title":"","metadata":{"abstract":"It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3\u0026#39;-azido-3\u0026#39;-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus ...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1997,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3\u0026#39;-azido-3\u0026#39;-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus ...","internal_url":"https://www.academia.edu/122873303/The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate","translated_internal_url":"","created_at":"2024-08-14T06:25:58.351-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":67401,"name":"Mutagenesis","url":"https://www.academia.edu/Documents/in/Mutagenesis"},{"id":74780,"name":"Mutation","url":"https://www.academia.edu/Documents/in/Mutation"},{"id":82145,"name":"Virus","url":"https://www.academia.edu/Documents/in/Virus"},{"id":502645,"name":"Retrovirus","url":"https://www.academia.edu/Documents/in/Retrovirus"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence"},{"id":1264920,"name":"Mutation Rate","url":"https://www.academia.edu/Documents/in/Mutation_Rate"},{"id":1622318,"name":"Antiviral Agents","url":"https://www.academia.edu/Documents/in/Antiviral_Agents"},{"id":2058615,"name":"Reticuloendotheliosis virus","url":"https://www.academia.edu/Documents/in/Reticuloendotheliosis_virus"},{"id":2467566,"name":"Molecular Sequence Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data"},{"id":2842083,"name":"Zalcitabine","url":"https://www.academia.edu/Documents/in/Zalcitabine"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"},{"id":4344744,"name":"Zidovudine","url":"https://www.academia.edu/Documents/in/Zidovudine"}],"urls":[{"id":44007075,"url":"https://journals.asm.org/doi/pdf/10.1128/jvi.71.6.4254-4263.1997"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873302"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873302/Homologous_recombination_occurs_in_a_distinct_retroviral_subpopulation_and_exhibits_high_negative_interference"><img alt="Research paper thumbnail of Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference" class="work-thumbnail" src="https://attachments.academia-assets.com/117443667/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873302/Homologous_recombination_occurs_in_a_distinct_retroviral_subpopulation_and_exhibits_high_negative_interference">Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1997</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Homologous recombination and deletions occur during retroviral replication when reverse transcrip...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Homologous recombination and deletions occur during retroviral replication when reverse transcriptase switches templates. While recombination occurs solely by intermolecular template switching (between copackaged RNAs), deletions can occur by an intermolecular or an intramolecular template switch (within the same RNA). To directly compare the rates of intramolecular and intermolecular template switching, two spleen necrosis virus-based vectors were constructed. Each vector contained a 110-bp direct repeat that was previously shown to delete at a high rate. The 110-bp direct repeat was flanked by two different sets of restriction site markers. These vectors were used to form heterozygotic virions containing RNAs of each parental vector, from which recombinant viruses were generated. By analyses of the markers flanking the direct repeats in recombinant and nonrecombinant proviruses, the rates of intramolecular and intermolecular template switching were determined. The results of these...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bdddd0e79fd981534ef652ac21c3cbc3" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443667,"asset_id":122873302,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443667/download_file?st=MTczMzM0ODY4NSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873302"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873302"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873302; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873302]").text(description); $(".js-view-count[data-work-id=122873302]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873302; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873302']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873302, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bdddd0e79fd981534ef652ac21c3cbc3" } } $('.js-work-strip[data-work-id=122873302]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873302,"title":"Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference","translated_title":"","metadata":{"abstract":"Homologous recombination and deletions occur during retroviral replication when reverse transcriptase switches templates. While recombination occurs solely by intermolecular template switching (between copackaged RNAs), deletions can occur by an intermolecular or an intramolecular template switch (within the same RNA). To directly compare the rates of intramolecular and intermolecular template switching, two spleen necrosis virus-based vectors were constructed. Each vector contained a 110-bp direct repeat that was previously shown to delete at a high rate. The 110-bp direct repeat was flanked by two different sets of restriction site markers. These vectors were used to form heterozygotic virions containing RNAs of each parental vector, from which recombinant viruses were generated. By analyses of the markers flanking the direct repeats in recombinant and nonrecombinant proviruses, the rates of intramolecular and intermolecular template switching were determined. The results of these...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1997,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Homologous recombination and deletions occur during retroviral replication when reverse transcriptase switches templates. While recombination occurs solely by intermolecular template switching (between copackaged RNAs), deletions can occur by an intermolecular or an intramolecular template switch (within the same RNA). To directly compare the rates of intramolecular and intermolecular template switching, two spleen necrosis virus-based vectors were constructed. Each vector contained a 110-bp direct repeat that was previously shown to delete at a high rate. The 110-bp direct repeat was flanked by two different sets of restriction site markers. These vectors were used to form heterozygotic virions containing RNAs of each parental vector, from which recombinant viruses were generated. By analyses of the markers flanking the direct repeats in recombinant and nonrecombinant proviruses, the rates of intramolecular and intermolecular template switching were determined. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873301"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873301/Development_of_Murine_Leukemia_Virus_Based_Self_Activating_Vectors_That_Efficiently_Delete_the_Selectable_Drug_Resistance_Gene_during_Reverse_Transcription"><img alt="Research paper thumbnail of Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873301/Development_of_Murine_Leukemia_Virus_Based_Self_Activating_Vectors_That_Efficiently_Delete_the_Selectable_Drug_Resistance_Gene_during_Reverse_Transcription">Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Expression of the selectable drug resistance gene in retroviral vectors used for gene therapy can...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Expression of the selectable drug resistance gene in retroviral vectors used for gene therapy can lead to a decreased expression of the gene of interest and may induce a host immune response, resulting in a decreased efficiency of gene therapy. In this study, we demonstrate that high-frequency deletion of direct repeats, an inherent property of reverse transcriptases, can be used to efficiently excise the drug resistance gene during reverse transcription. One retroviral vector containing a direct repeat deleted the neomycin resistance expression cassette during a single replication cycle at &gt;99% efficiency.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873301"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873301"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873301; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873301]").text(description); $(".js-view-count[data-work-id=122873301]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873301; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873301']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873301, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873301]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873301,"title":"Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription","translated_title":"","metadata":{"abstract":"Expression of the selectable drug resistance gene in retroviral vectors used for gene therapy can lead to a decreased expression of the gene of interest and may induce a host immune response, resulting in a decreased efficiency of gene therapy. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873300"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873300/Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis"><img alt="Research paper thumbnail of Relative Rates of Retroviral Reverse Transcriptase Template Switching during RNA- and DNA-Dependent DNA Synthesis" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873300/Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis">Relative Rates of Retroviral Reverse Transcriptase Template Switching during RNA- and DNA-Dependent DNA Synthesis</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1998</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which c...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which can result in mutations and recombination. The relative rates of in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are unknown. To determine the relative rates of RT template switching during copying of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral vectors containing a 400-bp direct repeat. The directly repeated sequences were upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct repeats flanked the PPT and attachment site ( att ) in the RB-LPL vector. RT template switching events could occur during either RNA- or DNA-dependent DNA synthesis and delete one copy of the direct repeat plus the intervening sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and DNA-dependent DNA synthesis generated viral DNA that could integrate into the host genome. However, any deletion of the direct repea...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873300"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873300"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873300; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873300]").text(description); $(".js-view-count[data-work-id=122873300]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873300; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873300']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873300, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873300]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873300,"title":"Relative Rates of Retroviral Reverse Transcriptase Template Switching during RNA- and DNA-Dependent DNA Synthesis","translated_title":"","metadata":{"abstract":"Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which can result in mutations and recombination. The relative rates of in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are unknown. To determine the relative rates of RT template switching during copying of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral vectors containing a 400-bp direct repeat. The directly repeated sequences were upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct repeats flanked the PPT and attachment site ( att ) in the RB-LPL vector. RT template switching events could occur during either RNA- or DNA-dependent DNA synthesis and delete one copy of the direct repeat plus the intervening sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and DNA-dependent DNA synthesis generated viral DNA that could integrate into the host genome. However, any deletion of the direct repea...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1998,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which can result in mutations and recombination. The relative rates of in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are unknown. To determine the relative rates of RT template switching during copying of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral vectors containing a 400-bp direct repeat. The directly repeated sequences were upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct repeats flanked the PPT and attachment site ( att ) in the RB-LPL vector. RT template switching events could occur during either RNA- or DNA-dependent DNA synthesis and delete one copy of the direct repeat plus the intervening sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and DNA-dependent DNA synthesis generated viral DNA that could integrate into the host genome. However, any deletion of the direct repea...","internal_url":"https://www.academia.edu/122873300/Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis","translated_internal_url":"","created_at":"2024-08-14T06:25:57.500-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":11929,"name":"DNA replication","url":"https://www.academia.edu/Documents/in/DNA_replication"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48057,"name":"DNA","url":"https://www.academia.edu/Documents/in/DNA"},{"id":53471,"name":"Relative Growth Rate","url":"https://www.academia.edu/Documents/in/Relative_Growth_Rate"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":2235833,"name":"Dna Synthesis","url":"https://www.academia.edu/Documents/in/Dna_Synthesis"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007072,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.72.6.5198-5206.1998"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873299"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873299/Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching"><img alt="Research paper thumbnail of Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873299/Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching">Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of rever...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was &gt;1,500 bp deleted at very high rates (&gt;90%). In contrast, vectors containing &lt;1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates withi...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873299"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873299"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873299; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873299]").text(description); $(".js-view-count[data-work-id=122873299]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873299; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873299']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873299, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873299]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873299,"title":"Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching","translated_title":"","metadata":{"abstract":"Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was \u0026gt;1,500 bp deleted at very high rates (\u0026gt;90%). In contrast, vectors containing \u0026lt;1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates withi...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1999,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was \u0026gt;1,500 bp deleted at very high rates (\u0026gt;90%). In contrast, vectors containing \u0026lt;1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates withi...","internal_url":"https://www.academia.edu/122873299/Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching","translated_internal_url":"","created_at":"2024-08-14T06:25:57.271-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":29082,"name":"Sequence Analysis","url":"https://www.academia.edu/Documents/in/Sequence_Analysis"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":627622,"name":"Thymidine Kinase","url":"https://www.academia.edu/Documents/in/Thymidine_Kinase"},{"id":663515,"name":"Homologous Recombination","url":"https://www.academia.edu/Documents/in/Homologous_Recombination"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007071,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.73.10.7923-7932.1999"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873298"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873298/Experimental_and_Kinetics_Studies_for_Biogas_Production_Using_Water_Hyacinth_Eichhornia_crassipes_Mart_Solms_and_Sugar_Mill_Effluent"><img alt="Research paper thumbnail of Experimental and Kinetics Studies for Biogas Production Using Water Hyacinth (Eichhornia crassipes [Mart.] Solms) and Sugar Mill Effluent" class="work-thumbnail" src="https://attachments.academia-assets.com/117443668/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873298/Experimental_and_Kinetics_Studies_for_Biogas_Production_Using_Water_Hyacinth_Eichhornia_crassipes_Mart_Solms_and_Sugar_Mill_Effluent">Experimental and Kinetics Studies for Biogas Production Using Water Hyacinth (Eichhornia crassipes [Mart.] Solms) and Sugar Mill Effluent</a></div><div class="wp-workCard_item"><span>Waste and Biomass Valorization</span><span>, 2018</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="aae27797b5a4c42c14163aa3aa83d2a3" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443668,"asset_id":122873298,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443668/download_file?st=MTczMzM0ODY4NSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873298"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873298"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873298; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873297"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873297/The_phosphorylation_state_of_eucaryotic_initiation_factor_2_alters_translational_efficiency_of_specific_mRNAs"><img alt="Research paper thumbnail of The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs" class="work-thumbnail" src="https://attachments.academia-assets.com/117443669/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873297/The_phosphorylation_state_of_eucaryotic_initiation_factor_2_alters_translational_efficiency_of_specific_mRNAs">The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs</a></div><div class="wp-workCard_item"><span>Molecular and Cellular Biology</span><span>, 1989</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. The importance of eIF-2 alpha phosphorylation in regulating translation was studied by expression of specific mutants of eIF-2 alpha in COS-1 cells. DNA transfection of certain plasmids could activate DAI kinase and result in poor translation of plasmid-derived mRNAs. In these cases, translation of the plasmid-derived mRNAs was improved by the presence of DAI kinase inhibitors or by the presence of a nonphosphorylatable mutant (serine to alanine) of eIF-2 alpha. The improved translation mediated by expression of the nonphosphorylatable eIF-2 alpha mutant was specific to plasmid-derived mRNA and did not affect global mRNA translation. Expression of a serine-to-aspartic acid mutant eIF-2 alpha, created to mimic the phosphorylated serine, inhibited translation of the mRNAs der...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b3fb604007217636270d02ed18d47b42" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443669,"asset_id":122873297,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443669/download_file?st=MTczMzM0ODY4NSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873297"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873297"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873297; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873297]").text(description); $(".js-view-count[data-work-id=122873297]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873297; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873297']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873297, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b3fb604007217636270d02ed18d47b42" } } $('.js-work-strip[data-work-id=122873297]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873297,"title":"The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs","translated_title":"","metadata":{"abstract":"Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. 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Recombination occurs during DNA synthesis, whereby reverse transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. 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</script> <div class="js-work-strip profile--work_container" data-work-id="122873290"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873290/Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision"><img alt="Research paper thumbnail of Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: Balance between RNase H activity and nucleotide excision" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873290/Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision">Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: Balance between RNase H activity and nucleotide excision</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Understanding the mechanisms of HIV-1 drug resistance is critical for developing more effective a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Understanding the mechanisms of HIV-1 drug resistance is critical for developing more effective antiretroviral agents and therapies. Based on our previously described dynamic copy-choice mechanism for retroviral recombination and our observations that nucleoside reverse transcriptase inhibitors (NRTIs) increase the frequency of reverse transcriptase template switching, we propose that an equilibrium exists between ( i ) NRTI incorporation, NRTI excision, and resumption of DNA synthesis and ( ii ) degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication. As predicted by this model, mutations in the RNase H domain that reduced the rate of RNA degradation conferred high-level resistance to 3′-azido-3′-deoxythymidine and 2,3-didehydro-2,3-dideoxythymidine by as much as 180- and 10-fold, respectively, by increasing the time available for excision of incorporated NRTIs from terminated primers. These results pro...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873290"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873290"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873290; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873290]").text(description); $(".js-view-count[data-work-id=122873290]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873290; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873290']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873290, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873290]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873290,"title":"Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: Balance between RNase H activity and nucleotide excision","translated_title":"","metadata":{"abstract":"Understanding the mechanisms of HIV-1 drug resistance is critical for developing more effective antiretroviral agents and therapies. Based on our previously described dynamic copy-choice mechanism for retroviral recombination and our observations that nucleoside reverse transcriptase inhibitors (NRTIs) increase the frequency of reverse transcriptase template switching, we propose that an equilibrium exists between ( i ) NRTI incorporation, NRTI excision, and resumption of DNA synthesis and ( ii ) degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication. As predicted by this model, mutations in the RNase H domain that reduced the rate of RNA degradation conferred high-level resistance to 3′-azido-3′-deoxythymidine and 2,3-didehydro-2,3-dideoxythymidine by as much as 180- and 10-fold, respectively, by increasing the time available for excision of incorporated NRTIs from terminated primers. 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As predicted by this model, mutations in the RNase H domain that reduced the rate of RNA degradation conferred high-level resistance to 3′-azido-3′-deoxythymidine and 2,3-didehydro-2,3-dideoxythymidine by as much as 180- and 10-fold, respectively, by increasing the time available for excision of incorporated NRTIs from terminated primers. These results pro...","internal_url":"https://www.academia.edu/122873290/Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision","translated_internal_url":"","created_at":"2024-08-14T06:25:48.440-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":23067,"name":"DNA repair","url":"https://www.academia.edu/Documents/in/DNA_repair"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":569028,"name":"Genetic Recombination","url":"https://www.academia.edu/Documents/in/Genetic_Recombination"},{"id":963360,"name":"Nucleosides","url":"https://www.academia.edu/Documents/in/Nucleosides"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":1622318,"name":"Antiviral Agents","url":"https://www.academia.edu/Documents/in/Antiviral_Agents"},{"id":2235833,"name":"Dna Synthesis","url":"https://www.academia.edu/Documents/in/Dna_Synthesis"},{"id":3853201,"name":"reverse transcriptase inhibitors","url":"https://www.academia.edu/Documents/in/reverse_transcriptase_inhibitors"},{"id":4344744,"name":"Zidovudine","url":"https://www.academia.edu/Documents/in/Zidovudine"}],"urls":[{"id":44007065,"url":"https://pnas.org/doi/pdf/10.1073/pnas.0409823102"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873289"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873289/Y586F_mutation_in_murine_leukemia_virus_reverse_transcriptase_decreases_fidelity_of_DNA_synthesis_in_regions_associated_with_adenine_thymine_tracts"><img alt="Research paper thumbnail of Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine–thymine tracts" class="work-thumbnail" src="https://attachments.academia-assets.com/117443663/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873289/Y586F_mutation_in_murine_leukemia_virus_reverse_transcriptase_decreases_fidelity_of_DNA_synthesis_in_regions_associated_with_adenine_thymine_tracts">Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine–thymine tracts</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein gen...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate ≈5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine–thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. The results suggest that wild-type reverse transcriptase (RT) facilitates a specific conformation of the template–primer duplex at the polymerase active site that is important for accuracy of DNA synthesis; when an adenine–thymine tract is within 18 nt of t...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2ba4dc46d98cdd572202493bc915d49d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443663,"asset_id":122873289,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443663/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873289"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873289"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873289; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873289]").text(description); $(".js-view-count[data-work-id=122873289]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873289; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873289']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873289, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "2ba4dc46d98cdd572202493bc915d49d" } } $('.js-work-strip[data-work-id=122873289]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873289,"title":"Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine–thymine tracts","translated_title":"","metadata":{"abstract":"Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate ≈5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine–thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. The results suggest that wild-type reverse transcriptase (RT) facilitates a specific conformation of the template–primer duplex at the polymerase active site that is important for accuracy of DNA synthesis; when an adenine–thymine tract is within 18 nt of t...","publisher":"Proceedings of the National Academy of Sciences","ai_title_tag":"Y586F Mutation in MLV RT Increases DNA Synthesis Errors","publication_date":{"day":null,"month":null,"year":2002,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":"Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate ≈5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine–thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. The results suggest that wild-type reverse transcriptase (RT) facilitates a specific conformation of the template–primer duplex at the polymerase active site that is important for accuracy of DNA synthesis; when an adenine–thymine tract is within 18 nt of 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Sequence","url":"https://www.academia.edu/Documents/in/Amino_Acid_Sequence"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence"},{"id":894908,"name":"Amino Acid Substitution Rates","url":"https://www.academia.edu/Documents/in/Amino_Acid_Substitution_Rates"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":1264920,"name":"Mutation Rate","url":"https://www.academia.edu/Documents/in/Mutation_Rate"},{"id":1581100,"name":"DNA Polymerase","url":"https://www.academia.edu/Documents/in/DNA_Polymerase"},{"id":2235833,"name":"Dna Synthesis","url":"https://www.academia.edu/Documents/in/Dna_Synthesis"},{"id":2467566,"name":"Molecular Sequence Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data"},{"id":3136073,"name":"Murine Leukemia 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/></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873288/Capsid_Proteins_from_Human_Immunodeficiency_Virus_Type_1_and_Simian_Immunodeficiency_Virus_SIV_mac_Can_Coassemble_into_Mature_Cores_of_Infectious_Viruses">Capsid Proteins from Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus SIV mac Can Coassemble into Mature Cores of Infectious Viruses</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1)...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV mac CA protein (sCA). If hCA and sCA cannot coassemble into the same cor...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873288"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873288"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873288; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873288]").text(description); $(".js-view-count[data-work-id=122873288]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873288; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873288']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873288, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873288]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873288,"title":"Capsid Proteins from Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus SIV mac Can Coassemble into Mature Cores of Infectious Viruses","translated_title":"","metadata":{"abstract":"We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV mac CA protein (sCA). If hCA and sCA cannot coassemble into the same cor...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV mac CA protein (sCA). If hCA and sCA cannot coassemble into the same cor...","internal_url":"https://www.academia.edu/122873288/Capsid_Proteins_from_Human_Immunodeficiency_Virus_Type_1_and_Simian_Immunodeficiency_Virus_SIV_mac_Can_Coassemble_into_Mature_Cores_of_Infectious_Viruses","translated_internal_url":"","created_at":"2024-08-14T06:25:47.751-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Capsid_Proteins_from_Human_Immunodeficiency_Virus_Type_1_and_Simian_Immunodeficiency_Virus_SIV_mac_Can_Coassemble_into_Mature_Cores_of_Infectious_Viruses","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":65127,"name":"J. Virol","url":"https://www.academia.edu/Documents/in/J._Virol"},{"id":71294,"name":"Kidney","url":"https://www.academia.edu/Documents/in/Kidney"},{"id":82145,"name":"Virus","url":"https://www.academia.edu/Documents/in/Virus"},{"id":190363,"name":"Plasmids","url":"https://www.academia.edu/Documents/in/Plasmids"},{"id":201140,"name":"Capsid","url":"https://www.academia.edu/Documents/in/Capsid"},{"id":620070,"name":"Transfection","url":"https://www.academia.edu/Documents/in/Transfection"},{"id":724924,"name":"Simian Immunodeficiency Virus","url":"https://www.academia.edu/Documents/in/Simian_Immunodeficiency_Virus"},{"id":1248637,"name":"Capsid Protein","url":"https://www.academia.edu/Documents/in/Capsid_Protein"},{"id":2420252,"name":"Infectivity","url":"https://www.academia.edu/Documents/in/Infectivity"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007063,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02663-07"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873287"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873287/Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination"><img alt="Research paper thumbnail of Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873287/Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination">Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor templ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor template can be the same RNA (intramolecular) or the copackaged RNA (intermolecular). Previous results indicated that intramolecular template switching occurred far more frequently than intermolecular template switching. We hypothesized that intermolecular template-switching events (recombination) occurred at a lower efficiency because the copackaged RNA was not accessible to the RT. To test our hypothesis, the murine leukemia virus (MLV) extended packaging signal (Ψ + ) containing a dimer linkage structure (DLS) was relocated from the 5′ untranslated region (UTR) to between selectable markers, allowing the two viral RNAs to interact closely in this region. It was found that the overall maximum recombination rates of vectors with Ψ + in the 5′ UTR or Ψ + between selectable markers were not drastically different. However, vectors with Ψ + located between selectable markers reached a plateau of...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873287"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873287"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873287; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873287]").text(description); $(".js-view-count[data-work-id=122873287]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873287; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873287']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873287, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873287]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873287,"title":"Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination","translated_title":"","metadata":{"abstract":"Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor template can be the same RNA (intramolecular) or the copackaged RNA (intermolecular). Previous results indicated that intramolecular template switching occurred far more frequently than intermolecular template switching. We hypothesized that intermolecular template-switching events (recombination) occurred at a lower efficiency because the copackaged RNA was not accessible to the RT. To test our hypothesis, the murine leukemia virus (MLV) extended packaging signal (Ψ + ) containing a dimer linkage structure (DLS) was relocated from the 5′ untranslated region (UTR) to between selectable markers, allowing the two viral RNAs to interact closely in this region. It was found that the overall maximum recombination rates of vectors with Ψ + in the 5′ UTR or Ψ + between selectable markers were not drastically different. However, vectors with Ψ + located between selectable markers reached a plateau of...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2000,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor template can be the same RNA (intramolecular) or the copackaged RNA (intermolecular). Previous results indicated that intramolecular template switching occurred far more frequently than intermolecular template switching. We hypothesized that intermolecular template-switching events (recombination) occurred at a lower efficiency because the copackaged RNA was not accessible to the RT. To test our hypothesis, the murine leukemia virus (MLV) extended packaging signal (Ψ + ) containing a dimer linkage structure (DLS) was relocated from the 5′ untranslated region (UTR) to between selectable markers, allowing the two viral RNAs to interact closely in this region. It was found that the overall maximum recombination rates of vectors with Ψ + in the 5′ UTR or Ψ + between selectable markers were not drastically different. However, vectors with Ψ + located between selectable markers reached a plateau of...","internal_url":"https://www.academia.edu/122873287/Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination","translated_internal_url":"","created_at":"2024-08-14T06:25:47.033-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics"},{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":118339,"name":"Polymerase Chain Reaction","url":"https://www.academia.edu/Documents/in/Polymerase_Chain_Reaction"},{"id":190363,"name":"Plasmids","url":"https://www.academia.edu/Documents/in/Plasmids"},{"id":569028,"name":"Genetic Recombination","url":"https://www.academia.edu/Documents/in/Genetic_Recombination"},{"id":620070,"name":"Transfection","url":"https://www.academia.edu/Documents/in/Transfection"},{"id":900154,"name":"Recombination","url":"https://www.academia.edu/Documents/in/Recombination"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":2579012,"name":"restriction enzyme","url":"https://www.academia.edu/Documents/in/restriction_enzyme"},{"id":2894265,"name":"Restriction Mapping","url":"https://www.academia.edu/Documents/in/Restriction_Mapping"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007062,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.74.15.6953-6963.2000"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873286"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873286/Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes"><img alt="Research paper thumbnail of Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes" class="work-thumbnail" src="https://attachments.academia-assets.com/117443662/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873286/Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes">Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-b...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312: 281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene ( GFP ), and a second PBS derived from HIV-2 3′ of GFP . Simultaneous initiation of reverse transcription at both the 5′ HIV-1 PBS and 3′ HIV-2 PBS was predicted to result in deletion of GFP . As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HI...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="cde4a2e7f6b61c757c8cdf5db8417dec" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443662,"asset_id":122873286,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443662/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873286"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873286"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873286; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873286]").text(description); $(".js-view-count[data-work-id=122873286]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873286; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873286']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873286, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "cde4a2e7f6b61c757c8cdf5db8417dec" } } $('.js-work-strip[data-work-id=122873286]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873286,"title":"Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes","translated_title":"","metadata":{"abstract":"We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312: 281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene ( GFP ), and a second PBS derived from HIV-2 3′ of GFP . Simultaneous initiation of reverse transcription at both the 5′ HIV-1 PBS and 3′ HIV-2 PBS was predicted to result in deletion of GFP . As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HI...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312: 281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene ( GFP ), and a second PBS derived from HIV-2 3′ of GFP . Simultaneous initiation of reverse transcription at both the 5′ HIV-1 PBS and 3′ HIV-2 PBS was predicted to result in deletion of GFP . As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HI...","internal_url":"https://www.academia.edu/122873286/Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes","translated_internal_url":"","created_at":"2024-08-14T06:25:46.653-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":117443662,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/117443662/thumbnails/1.jpg","file_name":"pathakjv78_5402.pdf","download_url":"https://www.academia.edu/attachments/117443662/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Frequent_Dual_Initiation_in_Human_Immuno.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/117443662/pathakjv78_5402-libre.pdf?1723642535=\u0026response-content-disposition=attachment%3B+filename%3DFrequent_Dual_Initiation_in_Human_Immuno.pdf\u0026Expires=1733352286\u0026Signature=WXjGD45fdwbDEGu3hrdTVJL0RbhueIUL17XgM95CdTXQtertvrnv6Js7v-GDhU7W02poCrxWulatmWbfIAtU3oD~Z3l~fcW74g4XkYSJThGdN616IL20AbV0MqFlNxZybfl0zVHnoPD57uVgCDoOgY-PdLsJYXb8MIXlV~YEy64FCynDMTXB-4lGVQl6KvNZKW4CsS-ylFby58-28QfU8OkSOsRXh7o79SSzhW2a0KRezDwOyvoIpfYC0pdR3ggnrxla2jO7ApIsdsJ5Wvh3u365r9jJn4sXoyvoFFxSPXpf089xYHYlhZAy1Kv6vSoJYIZsrHsLvpZ4Ldj1PkjFxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes","translated_slug":"","page_count":12,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[{"id":117443662,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/117443662/thumbnails/1.jpg","file_name":"pathakjv78_5402.pdf","download_url":"https://www.academia.edu/attachments/117443662/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Frequent_Dual_Initiation_in_Human_Immuno.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/117443662/pathakjv78_5402-libre.pdf?1723642535=\u0026response-content-disposition=attachment%3B+filename%3DFrequent_Dual_Initiation_in_Human_Immuno.pdf\u0026Expires=1733352286\u0026Signature=WXjGD45fdwbDEGu3hrdTVJL0RbhueIUL17XgM95CdTXQtertvrnv6Js7v-GDhU7W02poCrxWulatmWbfIAtU3oD~Z3l~fcW74g4XkYSJThGdN616IL20AbV0MqFlNxZybfl0zVHnoPD57uVgCDoOgY-PdLsJYXb8MIXlV~YEy64FCynDMTXB-4lGVQl6KvNZKW4CsS-ylFby58-28QfU8OkSOsRXh7o79SSzhW2a0KRezDwOyvoIpfYC0pdR3ggnrxla2jO7ApIsdsJ5Wvh3u365r9jJn4sXoyvoFFxSPXpf089xYHYlhZAy1Kv6vSoJYIZsrHsLvpZ4Ldj1PkjFxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":67401,"name":"Mutagenesis","url":"https://www.academia.edu/Documents/in/Mutagenesis"},{"id":118339,"name":"Polymerase Chain Reaction","url":"https://www.academia.edu/Documents/in/Polymerase_Chain_Reaction"},{"id":202410,"name":"Green Fluorescent Protein","url":"https://www.academia.edu/Documents/in/Green_Fluorescent_Protein"},{"id":318308,"name":"Human immunodeficiency virus","url":"https://www.academia.edu/Documents/in/Human_immunodeficiency_virus"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":2467566,"name":"Molecular Sequence Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data"},{"id":2898895,"name":"binding sites","url":"https://www.academia.edu/Documents/in/binding_sites"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873285"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873285/Determination_of_the_Ex_Vivo_Rates_of_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcription_by_Using_Novel_Strand_Specific_Amplification_Analysis"><img alt="Research paper thumbnail of Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis" class="work-thumbnail" src="https://attachments.academia-assets.com/117443672/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873285/Determination_of_the_Ex_Vivo_Rates_of_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcription_by_Using_Novel_Strand_Specific_Amplification_Analysis">Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesi...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4 + T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. Additionally, our results indicate that plus-strand DNA synthes...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1bda31e6892228f17c67915235412040" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443672,"asset_id":122873285,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443672/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873285"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873285"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873285; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873285]").text(description); $(".js-view-count[data-work-id=122873285]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873285; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873285']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873285, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1bda31e6892228f17c67915235412040" } } $('.js-work-strip[data-work-id=122873285]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873285,"title":"Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis","translated_title":"","metadata":{"abstract":"Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4 + T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. Additionally, our results indicate that plus-strand DNA synthes...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4 + T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873284"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873284/APOBEC3F_and_APOBEC3G_Inhibit_HIV_1_DNA_Integration_by_Different_Mechanisms"><img alt="Research paper thumbnail of APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873284/APOBEC3F_and_APOBEC3G_Inhibit_HIV_1_DNA_Integration_by_Different_Mechanisms">APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit hu...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81:7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. We further investigated the mechanisms by which A3F and A3G block viral DNA integration by analyzing their effects on viral cDNA processing using S...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873284"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873284"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873284; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873284]").text(description); $(".js-view-count[data-work-id=122873284]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873284; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873284']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873284, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873284]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873284,"title":"APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms","translated_title":"","metadata":{"abstract":"APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81:7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. We further investigated the mechanisms by which A3F and A3G block viral DNA integration by analyzing their effects on viral cDNA processing using S...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81:7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. We further investigated the mechanisms by which A3F and A3G block viral DNA integration by analyzing their effects on viral cDNA processing using S...","internal_url":"https://www.academia.edu/122873284/APOBEC3F_and_APOBEC3G_Inhibit_HIV_1_DNA_Integration_by_Different_Mechanisms","translated_internal_url":"","created_at":"2024-08-14T06:25:45.652-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"APOBEC3F_and_APOBEC3G_Inhibit_HIV_1_DNA_Integration_by_Different_Mechanisms","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48057,"name":"DNA","url":"https://www.academia.edu/Documents/in/DNA"},{"id":638554,"name":"Integrase","url":"https://www.academia.edu/Documents/in/Integrase"},{"id":1675445,"name":"Viral Replication","url":"https://www.academia.edu/Documents/in/Viral_Replication"},{"id":2940274,"name":"virus integration","url":"https://www.academia.edu/Documents/in/virus_integration"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007060,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02358-09"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="19905407" id="papers"><div class="js-work-strip profile--work_container" data-work-id="122873305"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873305/Survey_of_int_Region_DNA_Rearrangements_in_C3H_and_BALB_cfC3H_Mouse_Mammary_Tumor_System23"><img alt="Research paper thumbnail of Survey of int Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System23" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873305/Survey_of_int_Region_DNA_Rearrangements_in_C3H_and_BALB_cfC3H_Mouse_Mammary_Tumor_System23">Survey of int Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System23</a></div><div class="wp-workCard_item"><span>JNCI: Journal of the National Cancer Institute</span><span>, 1987</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BAL...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BALB/cfC3H hyperplastic alveolar nodule and its hyperplastic outgrowth (HPO) model systems by examining the DNA of the different stages of the neoplastic progression, with use of the Southern blot technique. Rearrangement of int region DNAs associated with proviral amplification occurred more frequently in spontaneous tumors (19 of 27) than in tumors from HPOs (7 of 37) and rarely occurred in HPOs (1 of 29). However, the int-1 rearrangement maintained in 1 BALB/cfC3H HPO line through 11 transplant generations suggests that the int-1 rearrangement is neither sufficient nor necessary for progression to mouse mammary carcinoma.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873305"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873305"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873305; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873305]").text(description); $(".js-view-count[data-work-id=122873305]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873305; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873305']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873305, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873305]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873305,"title":"Survey of int Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System23","translated_title":"","metadata":{"abstract":"Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BALB/cfC3H hyperplastic alveolar nodule and its hyperplastic outgrowth (HPO) model systems by examining the DNA of the different stages of the neoplastic progression, with use of the Southern blot technique. Rearrangement of int region DNAs associated with proviral amplification occurred more frequently in spontaneous tumors (19 of 27) than in tumors from HPOs (7 of 37) and rarely occurred in HPOs (1 of 29). However, the int-1 rearrangement maintained in 1 BALB/cfC3H HPO line through 11 transplant generations suggests that the int-1 rearrangement is neither sufficient nor necessary for progression to mouse mammary carcinoma.","publisher":"Oxford University Press (OUP)","publication_date":{"day":null,"month":null,"year":1987,"errors":{}},"publication_name":"JNCI: Journal of the National Cancer Institute"},"translated_abstract":"Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BALB/cfC3H hyperplastic alveolar nodule and its hyperplastic outgrowth (HPO) model systems by examining the DNA of the different stages of the neoplastic progression, with use of the Southern blot technique. Rearrangement of int region DNAs associated with proviral amplification occurred more frequently in spontaneous tumors (19 of 27) than in tumors from HPOs (7 of 37) and rarely occurred in HPOs (1 of 29). However, the int-1 rearrangement maintained in 1 BALB/cfC3H HPO line through 11 transplant generations suggests that the int-1 rearrangement is neither sufficient nor necessary for progression to mouse mammary carcinoma.","internal_url":"https://www.academia.edu/122873305/Survey_of_int_Region_DNA_Rearrangements_in_C3H_and_BALB_cfC3H_Mouse_Mammary_Tumor_System23","translated_internal_url":"","created_at":"2024-08-14T06:25:58.763-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Survey_of_int_Region_DNA_Rearrangements_in_C3H_and_BALB_cfC3H_Mouse_Mammary_Tumor_System23","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":48057,"name":"DNA","url":"https://www.academia.edu/Documents/in/DNA"},{"id":73949,"name":"Int","url":"https://www.academia.edu/Documents/in/Int"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":103360,"name":"Nucleic acid hybridization","url":"https://www.academia.edu/Documents/in/Nucleic_acid_hybridization"},{"id":203526,"name":"Neoplasm","url":"https://www.academia.edu/Documents/in/Neoplasm"},{"id":338613,"name":"Oncogenes","url":"https://www.academia.edu/Documents/in/Oncogenes"},{"id":375142,"name":"Precancerous Conditions","url":"https://www.academia.edu/Documents/in/Precancerous_Conditions"}],"urls":[{"id":44007076,"url":"http://academic.oup.com/jnci/article-pdf/78/2/327/2738254/78-2-327.pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873304"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873304/E_vectors_development_of_novel_self_inactivating_and_self_activating_retroviral_vectors_for_safer_gene_therapy"><img alt="Research paper thumbnail of E- vectors: development of novel self-inactivating and self-activating retroviral vectors for safer gene therapy" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873304/E_vectors_development_of_novel_self_inactivating_and_self_activating_retroviral_vectors_for_safer_gene_therapy">E- vectors: development of novel self-inactivating and self-activating retroviral vectors for safer gene therapy</a></div><div class="wp-workCard_item"><span>Journal of virology</span><span>, 1995</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We have developed novel self-inactivating and self-activating retroviral vectors based on the pre...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We have developed novel self-inactivating and self-activating retroviral vectors based on the previously observed high-frequency deletion of direct repeats. We constructed spleen necrosis virus (SNV)-based viral vectors that contained large direct repeats flanking the viral encapsidation sequence (E). A large proportion of the proviruses in the target cells had E and one copy of the direct repeat deleted. Direct repeats of 1,333 and 788 bp were deleted at frequencies of 93 and 85%, respectively. To achieve a 100% deletion efficiency in target cells after ex vivo infection and drug selection, we constructed a self-activating vector that simultaneously deleted E and reconstituted the neomycin phosphotransferase gene. Selection of the target cells for resistance to G418 (a neomycin analog) ensured that all integrated proviruses had E deleted. The proviruses with E deleted were mobilized by a replication-competent virus 267,000-fold less efficiently than proviruses with E. We named thes...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873304"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873304"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873304; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873304]").text(description); $(".js-view-count[data-work-id=122873304]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873304; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873304']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873304, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873304]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873304,"title":"E- vectors: development of novel self-inactivating and self-activating retroviral vectors for safer gene therapy","translated_title":"","metadata":{"abstract":"We have developed novel self-inactivating and self-activating retroviral vectors based on the previously observed high-frequency deletion of direct repeats. We constructed spleen necrosis virus (SNV)-based viral vectors that contained large direct repeats flanking the viral encapsidation sequence (E). A large proportion of the proviruses in the target cells had E and one copy of the direct repeat deleted. Direct repeats of 1,333 and 788 bp were deleted at frequencies of 93 and 85%, respectively. To achieve a 100% deletion efficiency in target cells after ex vivo infection and drug selection, we constructed a self-activating vector that simultaneously deleted E and reconstituted the neomycin phosphotransferase gene. Selection of the target cells for resistance to G418 (a neomycin analog) ensured that all integrated proviruses had E deleted. The proviruses with E deleted were mobilized by a replication-competent virus 267,000-fold less efficiently than proviruses with E. We named thes...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1995,"errors":{}},"publication_name":"Journal of virology"},"translated_abstract":"We have developed novel self-inactivating and self-activating retroviral vectors based on the previously observed high-frequency deletion of direct repeats. We constructed spleen necrosis virus (SNV)-based viral vectors that contained large direct repeats flanking the viral encapsidation sequence (E). A large proportion of the proviruses in the target cells had E and one copy of the direct repeat deleted. Direct repeats of 1,333 and 788 bp were deleted at frequencies of 93 and 85%, respectively. To achieve a 100% deletion efficiency in target cells after ex vivo infection and drug selection, we constructed a self-activating vector that simultaneously deleted E and reconstituted the neomycin phosphotransferase gene. Selection of the target cells for resistance to G418 (a neomycin analog) ensured that all integrated proviruses had E deleted. The proviruses with E deleted were mobilized by a replication-competent virus 267,000-fold less efficiently than proviruses with E. We named thes...","internal_url":"https://www.academia.edu/122873304/E_vectors_development_of_novel_self_inactivating_and_self_activating_retroviral_vectors_for_safer_gene_therapy","translated_internal_url":"","created_at":"2024-08-14T06:25:58.584-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"E_vectors_development_of_novel_self_inactivating_and_self_activating_retroviral_vectors_for_safer_gene_therapy","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":49161,"name":"Safety","url":"https://www.academia.edu/Documents/in/Safety"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":181936,"name":"Gene","url":"https://www.academia.edu/Documents/in/Gene"},{"id":295728,"name":"Molecular cloning","url":"https://www.academia.edu/Documents/in/Molecular_cloning"},{"id":620070,"name":"Transfection","url":"https://www.academia.edu/Documents/in/Transfection"},{"id":990417,"name":"Recombinant Proteins","url":"https://www.academia.edu/Documents/in/Recombinant_Proteins"},{"id":2894265,"name":"Restriction Mapping","url":"https://www.academia.edu/Documents/in/Restriction_Mapping"},{"id":2940274,"name":"virus integration","url":"https://www.academia.edu/Documents/in/virus_integration"},{"id":3061075,"name":"Genetic Therapy","url":"https://www.academia.edu/Documents/in/Genetic_Therapy"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873303"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873303/The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate"><img alt="Research paper thumbnail of The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873303/The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate">The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1997</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3&#39;-azido-3&#39;-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873303"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873303"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873303; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873303]").text(description); $(".js-view-count[data-work-id=122873303]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873303; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873303']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873303, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873303]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873303,"title":"The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate","translated_title":"","metadata":{"abstract":"It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3\u0026#39;-azido-3\u0026#39;-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus ...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1997,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3\u0026#39;-azido-3\u0026#39;-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus ...","internal_url":"https://www.academia.edu/122873303/The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate","translated_internal_url":"","created_at":"2024-08-14T06:25:58.351-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_antiretrovirus_drug_3_azido_3_deoxythymidine_increases_the_retrovirus_mutation_rate","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":67401,"name":"Mutagenesis","url":"https://www.academia.edu/Documents/in/Mutagenesis"},{"id":74780,"name":"Mutation","url":"https://www.academia.edu/Documents/in/Mutation"},{"id":82145,"name":"Virus","url":"https://www.academia.edu/Documents/in/Virus"},{"id":502645,"name":"Retrovirus","url":"https://www.academia.edu/Documents/in/Retrovirus"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence"},{"id":1264920,"name":"Mutation Rate","url":"https://www.academia.edu/Documents/in/Mutation_Rate"},{"id":1622318,"name":"Antiviral Agents","url":"https://www.academia.edu/Documents/in/Antiviral_Agents"},{"id":2058615,"name":"Reticuloendotheliosis virus","url":"https://www.academia.edu/Documents/in/Reticuloendotheliosis_virus"},{"id":2467566,"name":"Molecular Sequence Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data"},{"id":2842083,"name":"Zalcitabine","url":"https://www.academia.edu/Documents/in/Zalcitabine"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"},{"id":4344744,"name":"Zidovudine","url":"https://www.academia.edu/Documents/in/Zidovudine"}],"urls":[{"id":44007075,"url":"https://journals.asm.org/doi/pdf/10.1128/jvi.71.6.4254-4263.1997"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873302"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873302/Homologous_recombination_occurs_in_a_distinct_retroviral_subpopulation_and_exhibits_high_negative_interference"><img alt="Research paper thumbnail of Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference" class="work-thumbnail" src="https://attachments.academia-assets.com/117443667/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873302/Homologous_recombination_occurs_in_a_distinct_retroviral_subpopulation_and_exhibits_high_negative_interference">Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1997</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Homologous recombination and deletions occur during retroviral replication when reverse transcrip...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Homologous recombination and deletions occur during retroviral replication when reverse transcriptase switches templates. While recombination occurs solely by intermolecular template switching (between copackaged RNAs), deletions can occur by an intermolecular or an intramolecular template switch (within the same RNA). To directly compare the rates of intramolecular and intermolecular template switching, two spleen necrosis virus-based vectors were constructed. Each vector contained a 110-bp direct repeat that was previously shown to delete at a high rate. The 110-bp direct repeat was flanked by two different sets of restriction site markers. These vectors were used to form heterozygotic virions containing RNAs of each parental vector, from which recombinant viruses were generated. By analyses of the markers flanking the direct repeats in recombinant and nonrecombinant proviruses, the rates of intramolecular and intermolecular template switching were determined. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873301"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873301/Development_of_Murine_Leukemia_Virus_Based_Self_Activating_Vectors_That_Efficiently_Delete_the_Selectable_Drug_Resistance_Gene_during_Reverse_Transcription"><img alt="Research paper thumbnail of Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873301/Development_of_Murine_Leukemia_Virus_Based_Self_Activating_Vectors_That_Efficiently_Delete_the_Selectable_Drug_Resistance_Gene_during_Reverse_Transcription">Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Expression of the selectable drug resistance gene in retroviral vectors used for gene therapy can...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Expression of the selectable drug resistance gene in retroviral vectors used for gene therapy can lead to a decreased expression of the gene of interest and may induce a host immune response, resulting in a decreased efficiency of gene therapy. In this study, we demonstrate that high-frequency deletion of direct repeats, an inherent property of reverse transcriptases, can be used to efficiently excise the drug resistance gene during reverse transcription. One retroviral vector containing a direct repeat deleted the neomycin resistance expression cassette during a single replication cycle at &gt;99% efficiency.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873301"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873301"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873301; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873301]").text(description); $(".js-view-count[data-work-id=122873301]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873301; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873301']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873301, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873301]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873301,"title":"Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription","translated_title":"","metadata":{"abstract":"Expression of the selectable drug resistance gene in retroviral vectors used for gene therapy can lead to a decreased expression of the gene of interest and may induce a host immune response, resulting in a decreased efficiency of gene therapy. 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In this study, we demonstrate that high-frequency deletion of direct repeats, an inherent property of reverse transcriptases, can be used to efficiently excise the drug resistance gene during reverse transcription. One retroviral vector containing a direct repeat deleted the neomycin resistance expression cassette during a single replication cycle at \u0026gt;99% efficiency.","internal_url":"https://www.academia.edu/122873301/Development_of_Murine_Leukemia_Virus_Based_Self_Activating_Vectors_That_Efficiently_Delete_the_Selectable_Drug_Resistance_Gene_during_Reverse_Transcription","translated_internal_url":"","created_at":"2024-08-14T06:25:57.812-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Development_of_Murine_Leukemia_Virus_Based_Self_Activating_Vectors_That_Efficiently_Delete_the_Selectable_Drug_Resistance_Gene_during_Reverse_Transcription","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":2702,"name":"Immune response","url":"https://www.academia.edu/Documents/in/Immune_response"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":7864,"name":"Gene Therapy","url":"https://www.academia.edu/Documents/in/Gene_Therapy"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":27784,"name":"Gene expression","url":"https://www.academia.edu/Documents/in/Gene_expression"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48458,"name":"High Frequency","url":"https://www.academia.edu/Documents/in/High_Frequency"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":111011,"name":"Gene transfer techniques","url":"https://www.academia.edu/Documents/in/Gene_transfer_techniques"},{"id":181936,"name":"Gene","url":"https://www.academia.edu/Documents/in/Gene"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":1035358,"name":"Translational Control","url":"https://www.academia.edu/Documents/in/Translational_Control"},{"id":1567378,"name":"Internal ribosome entry site","url":"https://www.academia.edu/Documents/in/Internal_ribosome_entry_site"},{"id":3061075,"name":"Genetic Therapy","url":"https://www.academia.edu/Documents/in/Genetic_Therapy"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"},{"id":4098675,"name":"selectable marker ","url":"https://www.academia.edu/Documents/in/selectable_marker"}],"urls":[{"id":44007073,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.73.10.8837-8842.1999"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873300"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873300/Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis"><img alt="Research paper thumbnail of Relative Rates of Retroviral Reverse Transcriptase Template Switching during RNA- and DNA-Dependent DNA Synthesis" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873300/Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis">Relative Rates of Retroviral Reverse Transcriptase Template Switching during RNA- and DNA-Dependent DNA Synthesis</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1998</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which c...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which can result in mutations and recombination. The relative rates of in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are unknown. To determine the relative rates of RT template switching during copying of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral vectors containing a 400-bp direct repeat. The directly repeated sequences were upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct repeats flanked the PPT and attachment site ( att ) in the RB-LPL vector. RT template switching events could occur during either RNA- or DNA-dependent DNA synthesis and delete one copy of the direct repeat plus the intervening sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and DNA-dependent DNA synthesis generated viral DNA that could integrate into the host genome. However, any deletion of the direct repea...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873300"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873300"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873300; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873300]").text(description); $(".js-view-count[data-work-id=122873300]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873300; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873300']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873300, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873300]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873300,"title":"Relative Rates of Retroviral Reverse Transcriptase Template Switching during RNA- and DNA-Dependent DNA Synthesis","translated_title":"","metadata":{"abstract":"Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which can result in mutations and recombination. The relative rates of in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are unknown. To determine the relative rates of RT template switching during copying of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral vectors containing a 400-bp direct repeat. The directly repeated sequences were upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct repeats flanked the PPT and attachment site ( att ) in the RB-LPL vector. RT template switching events could occur during either RNA- or DNA-dependent DNA synthesis and delete one copy of the direct repeat plus the intervening sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and DNA-dependent DNA synthesis generated viral DNA that could integrate into the host genome. However, any deletion of the direct repea...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1998,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Retroviral reverse transcriptases (RTs) frequently switch templates during DNA synthesis, which can result in mutations and recombination. The relative rates of in vivo RT template switching during RNA- and DNA-dependent DNA synthesis are unknown. To determine the relative rates of RT template switching during copying of RNA and DNA templates, we constructed spleen necrosis virus-based retroviral vectors containing a 400-bp direct repeat. The directly repeated sequences were upstream of the polypurine tract (PPT) in the RB-LLP vector; the same direct repeats flanked the PPT and attachment site ( att ) in the RB-LPL vector. RT template switching events could occur during either RNA- or DNA-dependent DNA synthesis and delete one copy of the direct repeat plus the intervening sequences. RB-LLP vectors that underwent direct repeat deletions during RNA- and DNA-dependent DNA synthesis generated viral DNA that could integrate into the host genome. However, any deletion of the direct repea...","internal_url":"https://www.academia.edu/122873300/Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis","translated_internal_url":"","created_at":"2024-08-14T06:25:57.500-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Relative_Rates_of_Retroviral_Reverse_Transcriptase_Template_Switching_during_RNA_and_DNA_Dependent_DNA_Synthesis","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":11929,"name":"DNA replication","url":"https://www.academia.edu/Documents/in/DNA_replication"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48057,"name":"DNA","url":"https://www.academia.edu/Documents/in/DNA"},{"id":53471,"name":"Relative Growth Rate","url":"https://www.academia.edu/Documents/in/Relative_Growth_Rate"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":2235833,"name":"Dna Synthesis","url":"https://www.academia.edu/Documents/in/Dna_Synthesis"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007072,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.72.6.5198-5206.1998"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873299"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873299/Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching"><img alt="Research paper thumbnail of Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873299/Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching">Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of rever...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was &gt;1,500 bp deleted at very high rates (&gt;90%). In contrast, vectors containing &lt;1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates withi...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873299"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873299"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873299; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873299]").text(description); $(".js-view-count[data-work-id=122873299]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873299; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873299']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873299, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873299]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873299,"title":"Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching","translated_title":"","metadata":{"abstract":"Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was \u0026gt;1,500 bp deleted at very high rates (\u0026gt;90%). In contrast, vectors containing \u0026lt;1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates withi...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":1999,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was \u0026gt;1,500 bp deleted at very high rates (\u0026gt;90%). In contrast, vectors containing \u0026lt;1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates withi...","internal_url":"https://www.academia.edu/122873299/Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching","translated_internal_url":"","created_at":"2024-08-14T06:25:57.271-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effect_of_Distance_between_Homologous_Sequences_and_3_Homology_on_the_Frequency_of_Retroviral_Reverse_Transcriptase_Template_Switching","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":29082,"name":"Sequence Analysis","url":"https://www.academia.edu/Documents/in/Sequence_Analysis"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":627622,"name":"Thymidine Kinase","url":"https://www.academia.edu/Documents/in/Thymidine_Kinase"},{"id":663515,"name":"Homologous Recombination","url":"https://www.academia.edu/Documents/in/Homologous_Recombination"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007071,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.73.10.7923-7932.1999"}]}, dispatcherData: dispatcherData }); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873297"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873297/The_phosphorylation_state_of_eucaryotic_initiation_factor_2_alters_translational_efficiency_of_specific_mRNAs"><img alt="Research paper thumbnail of The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs" class="work-thumbnail" src="https://attachments.academia-assets.com/117443669/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873297/The_phosphorylation_state_of_eucaryotic_initiation_factor_2_alters_translational_efficiency_of_specific_mRNAs">The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs</a></div><div class="wp-workCard_item"><span>Molecular and Cellular Biology</span><span>, 1989</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. The importance of eIF-2 alpha phosphorylation in regulating translation was studied by expression of specific mutants of eIF-2 alpha in COS-1 cells. DNA transfection of certain plasmids could activate DAI kinase and result in poor translation of plasmid-derived mRNAs. In these cases, translation of the plasmid-derived mRNAs was improved by the presence of DAI kinase inhibitors or by the presence of a nonphosphorylatable mutant (serine to alanine) of eIF-2 alpha. The improved translation mediated by expression of the nonphosphorylatable eIF-2 alpha mutant was specific to plasmid-derived mRNA and did not affect global mRNA translation. Expression of a serine-to-aspartic acid mutant eIF-2 alpha, created to mimic the phosphorylated serine, inhibited translation of the mRNAs der...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b3fb604007217636270d02ed18d47b42" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443669,"asset_id":122873297,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443669/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4NSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873297"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873297"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873297; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873297]").text(description); $(".js-view-count[data-work-id=122873297]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873297; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873297']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873297, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b3fb604007217636270d02ed18d47b42" } } $('.js-work-strip[data-work-id=122873297]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873297,"title":"The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs","translated_title":"","metadata":{"abstract":"Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. 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href="https://www.academia.edu/122873291/Recombinant_Origin_of_the_Retrovirus_XMRV"><img alt="Research paper thumbnail of Recombinant Origin of the Retrovirus XMRV" class="work-thumbnail" src="https://attachments.academia-assets.com/117443898/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873291/Recombinant_Origin_of_the_Retrovirus_XMRV">Recombinant Origin of the Retrovirus XMRV</a></div><div class="wp-workCard_item"><span>Science</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Analysis of the origin of XMRV suggests that links between the virus and human disease are due to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Analysis of the origin of XMRV suggests that links between the virus and human disease are due to laboratory contamination.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b35431caefdcc2697d10594909ef27ce" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443898,"asset_id":122873291,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443898/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span 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</script> <div class="js-work-strip profile--work_container" data-work-id="122873290"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873290/Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision"><img alt="Research paper thumbnail of Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: Balance between RNase H activity and nucleotide excision" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873290/Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision">Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: Balance between RNase H activity and nucleotide excision</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Understanding the mechanisms of HIV-1 drug resistance is critical for developing more effective a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Understanding the mechanisms of HIV-1 drug resistance is critical for developing more effective antiretroviral agents and therapies. Based on our previously described dynamic copy-choice mechanism for retroviral recombination and our observations that nucleoside reverse transcriptase inhibitors (NRTIs) increase the frequency of reverse transcriptase template switching, we propose that an equilibrium exists between ( i ) NRTI incorporation, NRTI excision, and resumption of DNA synthesis and ( ii ) degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication. As predicted by this model, mutations in the RNase H domain that reduced the rate of RNA degradation conferred high-level resistance to 3′-azido-3′-deoxythymidine and 2,3-didehydro-2,3-dideoxythymidine by as much as 180- and 10-fold, respectively, by increasing the time available for excision of incorporated NRTIs from terminated primers. 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Based on our previously described dynamic copy-choice mechanism for retroviral recombination and our observations that nucleoside reverse transcriptase inhibitors (NRTIs) increase the frequency of reverse transcriptase template switching, we propose that an equilibrium exists between ( i ) NRTI incorporation, NRTI excision, and resumption of DNA synthesis and ( ii ) degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication. As predicted by this model, mutations in the RNase H domain that reduced the rate of RNA degradation conferred high-level resistance to 3′-azido-3′-deoxythymidine and 2,3-didehydro-2,3-dideoxythymidine by as much as 180- and 10-fold, respectively, by increasing the time available for excision of incorporated NRTIs from terminated primers. These results pro...","publisher":"Proceedings of the National Academy of Sciences","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":"Understanding the mechanisms of HIV-1 drug resistance is critical for developing more effective antiretroviral agents and therapies. Based on our previously described dynamic copy-choice mechanism for retroviral recombination and our observations that nucleoside reverse transcriptase inhibitors (NRTIs) increase the frequency of reverse transcriptase template switching, we propose that an equilibrium exists between ( i ) NRTI incorporation, NRTI excision, and resumption of DNA synthesis and ( ii ) degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication. As predicted by this model, mutations in the RNase H domain that reduced the rate of RNA degradation conferred high-level resistance to 3′-azido-3′-deoxythymidine and 2,3-didehydro-2,3-dideoxythymidine by as much as 180- and 10-fold, respectively, by increasing the time available for excision of incorporated NRTIs from terminated primers. These results pro...","internal_url":"https://www.academia.edu/122873290/Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision","translated_internal_url":"","created_at":"2024-08-14T06:25:48.440-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Mechanism_for_nucleoside_analog_mediated_abrogation_of_HIV_1_replication_Balance_between_RNase_H_activity_and_nucleotide_excision","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":23067,"name":"DNA repair","url":"https://www.academia.edu/Documents/in/DNA_repair"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":569028,"name":"Genetic Recombination","url":"https://www.academia.edu/Documents/in/Genetic_Recombination"},{"id":963360,"name":"Nucleosides","url":"https://www.academia.edu/Documents/in/Nucleosides"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":1622318,"name":"Antiviral Agents","url":"https://www.academia.edu/Documents/in/Antiviral_Agents"},{"id":2235833,"name":"Dna Synthesis","url":"https://www.academia.edu/Documents/in/Dna_Synthesis"},{"id":3853201,"name":"reverse transcriptase inhibitors","url":"https://www.academia.edu/Documents/in/reverse_transcriptase_inhibitors"},{"id":4344744,"name":"Zidovudine","url":"https://www.academia.edu/Documents/in/Zidovudine"}],"urls":[{"id":44007065,"url":"https://pnas.org/doi/pdf/10.1073/pnas.0409823102"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873289"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873289/Y586F_mutation_in_murine_leukemia_virus_reverse_transcriptase_decreases_fidelity_of_DNA_synthesis_in_regions_associated_with_adenine_thymine_tracts"><img alt="Research paper thumbnail of Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine–thymine tracts" class="work-thumbnail" src="https://attachments.academia-assets.com/117443663/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873289/Y586F_mutation_in_murine_leukemia_virus_reverse_transcriptase_decreases_fidelity_of_DNA_synthesis_in_regions_associated_with_adenine_thymine_tracts">Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine–thymine tracts</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein gen...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate ≈5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine–thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. The results suggest that wild-type reverse transcriptase (RT) facilitates a specific conformation of the template–primer duplex at the polymerase active site that is important for accuracy of DNA synthesis; when an adenine–thymine tract is within 18 nt of t...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2ba4dc46d98cdd572202493bc915d49d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443663,"asset_id":122873289,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443663/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873289"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873289"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873289; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873289]").text(description); $(".js-view-count[data-work-id=122873289]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873289; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873289']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873289, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "2ba4dc46d98cdd572202493bc915d49d" } } $('.js-work-strip[data-work-id=122873289]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873289,"title":"Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine–thymine tracts","translated_title":"","metadata":{"abstract":"Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate ≈5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine–thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. The results suggest that wild-type reverse transcriptase (RT) facilitates a specific conformation of the template–primer duplex at the polymerase active site that is important for accuracy of DNA synthesis; when an adenine–thymine tract is within 18 nt of t...","publisher":"Proceedings of the National Academy of Sciences","ai_title_tag":"Y586F Mutation in MLV RT Increases DNA Synthesis Errors","publication_date":{"day":null,"month":null,"year":2002,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":"Using in vivo fidelity assays in which bacterial β-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate ≈5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine–thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. 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/></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873288/Capsid_Proteins_from_Human_Immunodeficiency_Virus_Type_1_and_Simian_Immunodeficiency_Virus_SIV_mac_Can_Coassemble_into_Mature_Cores_of_Infectious_Viruses">Capsid Proteins from Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus SIV mac Can Coassemble into Mature Cores of Infectious Viruses</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1)...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV mac CA protein (sCA). If hCA and sCA cannot coassemble into the same cor...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873288"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873288"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873288; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873288]").text(description); $(".js-view-count[data-work-id=122873288]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873288; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873288']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873288, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873288]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873288,"title":"Capsid Proteins from Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus SIV mac Can Coassemble into Mature Cores of Infectious Viruses","translated_title":"","metadata":{"abstract":"We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV mac CA protein (sCA). If hCA and sCA cannot coassemble into the same cor...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV mac CA protein (sCA). If hCA and sCA cannot coassemble into the same cor...","internal_url":"https://www.academia.edu/122873288/Capsid_Proteins_from_Human_Immunodeficiency_Virus_Type_1_and_Simian_Immunodeficiency_Virus_SIV_mac_Can_Coassemble_into_Mature_Cores_of_Infectious_Viruses","translated_internal_url":"","created_at":"2024-08-14T06:25:47.751-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Capsid_Proteins_from_Human_Immunodeficiency_Virus_Type_1_and_Simian_Immunodeficiency_Virus_SIV_mac_Can_Coassemble_into_Mature_Cores_of_Infectious_Viruses","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":65127,"name":"J. Virol","url":"https://www.academia.edu/Documents/in/J._Virol"},{"id":71294,"name":"Kidney","url":"https://www.academia.edu/Documents/in/Kidney"},{"id":82145,"name":"Virus","url":"https://www.academia.edu/Documents/in/Virus"},{"id":190363,"name":"Plasmids","url":"https://www.academia.edu/Documents/in/Plasmids"},{"id":201140,"name":"Capsid","url":"https://www.academia.edu/Documents/in/Capsid"},{"id":620070,"name":"Transfection","url":"https://www.academia.edu/Documents/in/Transfection"},{"id":724924,"name":"Simian Immunodeficiency Virus","url":"https://www.academia.edu/Documents/in/Simian_Immunodeficiency_Virus"},{"id":1248637,"name":"Capsid Protein","url":"https://www.academia.edu/Documents/in/Capsid_Protein"},{"id":2420252,"name":"Infectivity","url":"https://www.academia.edu/Documents/in/Infectivity"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007063,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02663-07"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873287"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873287/Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination"><img alt="Research paper thumbnail of Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873287/Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination">Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor templ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor template can be the same RNA (intramolecular) or the copackaged RNA (intermolecular). Previous results indicated that intramolecular template switching occurred far more frequently than intermolecular template switching. We hypothesized that intermolecular template-switching events (recombination) occurred at a lower efficiency because the copackaged RNA was not accessible to the RT. To test our hypothesis, the murine leukemia virus (MLV) extended packaging signal (Ψ + ) containing a dimer linkage structure (DLS) was relocated from the 5′ untranslated region (UTR) to between selectable markers, allowing the two viral RNAs to interact closely in this region. It was found that the overall maximum recombination rates of vectors with Ψ + in the 5′ UTR or Ψ + between selectable markers were not drastically different. However, vectors with Ψ + located between selectable markers reached a plateau of...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873287"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873287"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873287; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873287]").text(description); $(".js-view-count[data-work-id=122873287]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873287; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873287']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873287, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873287]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873287,"title":"Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination","translated_title":"","metadata":{"abstract":"Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor template can be the same RNA (intramolecular) or the copackaged RNA (intermolecular). Previous results indicated that intramolecular template switching occurred far more frequently than intermolecular template switching. We hypothesized that intermolecular template-switching events (recombination) occurred at a lower efficiency because the copackaged RNA was not accessible to the RT. To test our hypothesis, the murine leukemia virus (MLV) extended packaging signal (Ψ + ) containing a dimer linkage structure (DLS) was relocated from the 5′ untranslated region (UTR) to between selectable markers, allowing the two viral RNAs to interact closely in this region. It was found that the overall maximum recombination rates of vectors with Ψ + in the 5′ UTR or Ψ + between selectable markers were not drastically different. However, vectors with Ψ + located between selectable markers reached a plateau of...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2000,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Reverse transcriptase (RT) switches templates frequently during DNA synthesis; the acceptor template can be the same RNA (intramolecular) or the copackaged RNA (intermolecular). Previous results indicated that intramolecular template switching occurred far more frequently than intermolecular template switching. We hypothesized that intermolecular template-switching events (recombination) occurred at a lower efficiency because the copackaged RNA was not accessible to the RT. To test our hypothesis, the murine leukemia virus (MLV) extended packaging signal (Ψ + ) containing a dimer linkage structure (DLS) was relocated from the 5′ untranslated region (UTR) to between selectable markers, allowing the two viral RNAs to interact closely in this region. It was found that the overall maximum recombination rates of vectors with Ψ + in the 5′ UTR or Ψ + between selectable markers were not drastically different. However, vectors with Ψ + located between selectable markers reached a plateau of...","internal_url":"https://www.academia.edu/122873287/Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination","translated_internal_url":"","created_at":"2024-08-14T06:25:47.033-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effect_of_the_Murine_Leukemia_Virus_Extended_Packaging_Signal_on_the_Rates_and_Locations_of_Retroviral_Recombination","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[],"research_interests":[{"id":156,"name":"Genetics","url":"https://www.academia.edu/Documents/in/Genetics"},{"id":3701,"name":"RNA","url":"https://www.academia.edu/Documents/in/RNA"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":118339,"name":"Polymerase Chain Reaction","url":"https://www.academia.edu/Documents/in/Polymerase_Chain_Reaction"},{"id":190363,"name":"Plasmids","url":"https://www.academia.edu/Documents/in/Plasmids"},{"id":569028,"name":"Genetic Recombination","url":"https://www.academia.edu/Documents/in/Genetic_Recombination"},{"id":620070,"name":"Transfection","url":"https://www.academia.edu/Documents/in/Transfection"},{"id":900154,"name":"Recombination","url":"https://www.academia.edu/Documents/in/Recombination"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":2579012,"name":"restriction enzyme","url":"https://www.academia.edu/Documents/in/restriction_enzyme"},{"id":2894265,"name":"Restriction Mapping","url":"https://www.academia.edu/Documents/in/Restriction_Mapping"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[{"id":44007062,"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.74.15.6953-6963.2000"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873286"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873286/Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes"><img alt="Research paper thumbnail of Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes" class="work-thumbnail" src="https://attachments.academia-assets.com/117443662/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873286/Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes">Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-b...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312: 281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene ( GFP ), and a second PBS derived from HIV-2 3′ of GFP . Simultaneous initiation of reverse transcription at both the 5′ HIV-1 PBS and 3′ HIV-2 PBS was predicted to result in deletion of GFP . As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HI...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="cde4a2e7f6b61c757c8cdf5db8417dec" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443662,"asset_id":122873286,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443662/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873286"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873286"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873286; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873286]").text(description); $(".js-view-count[data-work-id=122873286]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873286; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873286']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873286, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "cde4a2e7f6b61c757c8cdf5db8417dec" } } $('.js-work-strip[data-work-id=122873286]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873286,"title":"Frequent Dual Initiation in Human Immunodeficiency Virus-Based Vectors Containing Two Primer-Binding Sites: a Quantitative In Vivo Assay for Function of Initiation Complexes","translated_title":"","metadata":{"abstract":"We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312: 281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene ( GFP ), and a second PBS derived from HIV-2 3′ of GFP . Simultaneous initiation of reverse transcription at both the 5′ HIV-1 PBS and 3′ HIV-2 PBS was predicted to result in deletion of GFP . As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HI...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312: 281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene ( GFP ), and a second PBS derived from HIV-2 3′ of GFP . Simultaneous initiation of reverse transcription at both the 5′ HIV-1 PBS and 3′ HIV-2 PBS was predicted to result in deletion of GFP . As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HI...","internal_url":"https://www.academia.edu/122873286/Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes","translated_internal_url":"","created_at":"2024-08-14T06:25:46.653-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":117443662,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/117443662/thumbnails/1.jpg","file_name":"pathakjv78_5402.pdf","download_url":"https://www.academia.edu/attachments/117443662/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Frequent_Dual_Initiation_in_Human_Immuno.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/117443662/pathakjv78_5402-libre.pdf?1723642535=\u0026response-content-disposition=attachment%3B+filename%3DFrequent_Dual_Initiation_in_Human_Immuno.pdf\u0026Expires=1733352286\u0026Signature=WXjGD45fdwbDEGu3hrdTVJL0RbhueIUL17XgM95CdTXQtertvrnv6Js7v-GDhU7W02poCrxWulatmWbfIAtU3oD~Z3l~fcW74g4XkYSJThGdN616IL20AbV0MqFlNxZybfl0zVHnoPD57uVgCDoOgY-PdLsJYXb8MIXlV~YEy64FCynDMTXB-4lGVQl6KvNZKW4CsS-ylFby58-28QfU8OkSOsRXh7o79SSzhW2a0KRezDwOyvoIpfYC0pdR3ggnrxla2jO7ApIsdsJ5Wvh3u365r9jJn4sXoyvoFFxSPXpf089xYHYlhZAy1Kv6vSoJYIZsrHsLvpZ4Ldj1PkjFxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Frequent_Dual_Initiation_in_Human_Immunodeficiency_Virus_Based_Vectors_Containing_Two_Primer_Binding_Sites_a_Quantitative_In_Vivo_Assay_for_Function_of_Initiation_Complexes","translated_slug":"","page_count":12,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay Pathak","url":"https://mu.academia.edu/VinayPathak"},"attachments":[{"id":117443662,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/117443662/thumbnails/1.jpg","file_name":"pathakjv78_5402.pdf","download_url":"https://www.academia.edu/attachments/117443662/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Frequent_Dual_Initiation_in_Human_Immuno.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/117443662/pathakjv78_5402-libre.pdf?1723642535=\u0026response-content-disposition=attachment%3B+filename%3DFrequent_Dual_Initiation_in_Human_Immuno.pdf\u0026Expires=1733352286\u0026Signature=WXjGD45fdwbDEGu3hrdTVJL0RbhueIUL17XgM95CdTXQtertvrnv6Js7v-GDhU7W02poCrxWulatmWbfIAtU3oD~Z3l~fcW74g4XkYSJThGdN616IL20AbV0MqFlNxZybfl0zVHnoPD57uVgCDoOgY-PdLsJYXb8MIXlV~YEy64FCynDMTXB-4lGVQl6KvNZKW4CsS-ylFby58-28QfU8OkSOsRXh7o79SSzhW2a0KRezDwOyvoIpfYC0pdR3ggnrxla2jO7ApIsdsJ5Wvh3u365r9jJn4sXoyvoFFxSPXpf089xYHYlhZAy1Kv6vSoJYIZsrHsLvpZ4Ldj1PkjFxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":8089,"name":"Virology","url":"https://www.academia.edu/Documents/in/Virology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":39978,"name":"HIV","url":"https://www.academia.edu/Documents/in/HIV"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":67401,"name":"Mutagenesis","url":"https://www.academia.edu/Documents/in/Mutagenesis"},{"id":118339,"name":"Polymerase Chain Reaction","url":"https://www.academia.edu/Documents/in/Polymerase_Chain_Reaction"},{"id":202410,"name":"Green Fluorescent Protein","url":"https://www.academia.edu/Documents/in/Green_Fluorescent_Protein"},{"id":318308,"name":"Human immunodeficiency virus","url":"https://www.academia.edu/Documents/in/Human_immunodeficiency_virus"},{"id":809882,"name":"Base Sequence","url":"https://www.academia.edu/Documents/in/Base_Sequence"},{"id":973494,"name":"Reverse Transcriptase","url":"https://www.academia.edu/Documents/in/Reverse_Transcriptase"},{"id":2467566,"name":"Molecular Sequence Data","url":"https://www.academia.edu/Documents/in/Molecular_Sequence_Data"},{"id":2898895,"name":"binding sites","url":"https://www.academia.edu/Documents/in/binding_sites"},{"id":3136073,"name":"Murine Leukemia Virus","url":"https://www.academia.edu/Documents/in/Murine_Leukemia_Virus"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873285"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873285/Determination_of_the_Ex_Vivo_Rates_of_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcription_by_Using_Novel_Strand_Specific_Amplification_Analysis"><img alt="Research paper thumbnail of Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis" class="work-thumbnail" src="https://attachments.academia-assets.com/117443672/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873285/Determination_of_the_Ex_Vivo_Rates_of_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcription_by_Using_Novel_Strand_Specific_Amplification_Analysis">Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesi...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4 + T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. Additionally, our results indicate that plus-strand DNA synthes...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1bda31e6892228f17c67915235412040" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":117443672,"asset_id":122873285,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/117443672/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873285"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873285"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873285; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873285]").text(description); $(".js-view-count[data-work-id=122873285]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873285; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873285']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873285, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1bda31e6892228f17c67915235412040" } } $('.js-work-strip[data-work-id=122873285]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873285,"title":"Determination of the Ex Vivo Rates of Human Immunodeficiency Virus Type 1 Reverse Transcription by Using Novel Strand-Specific Amplification Analysis","translated_title":"","metadata":{"abstract":"Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4 + T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. Additionally, our results indicate that plus-strand DNA synthes...","publisher":"American Society for Microbiology","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Journal of Virology"},"translated_abstract":"Replication of human immunodeficiency virus type 1 (HIV-1), like all organisms, involves synthesis of a minus-strand and a plus-strand of nucleic acid. Currently available PCR methods cannot distinguish between the two strands of nucleic acids. To carry out detailed analysis of HIV-1 reverse transcription from infected cells, we have developed a novel strand-specific amplification (SSA) assay using single-stranded padlock probes that are specifically hybridized to a target strand, ligated, and quantified for sensitive analysis of the kinetics of HIV-1 reverse transcription in cells. Using SSA, we have determined for the first time the ex vivo rates of HIV-1 minus-strand DNA synthesis in 293T and human primary CD4 + T cells (∼68 to 70 nucleotides/min). We also determined the rates of minus-strand DNA transfer (∼4 min), plus-strand DNA transfer (∼26 min), and initiation of plus-strand DNA synthesis (∼9 min) in 293T cells. Additionally, our results indicate that plus-strand DNA synthes...","internal_url":"https://www.academia.edu/122873285/Determination_of_the_Ex_Vivo_Rates_of_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcription_by_Using_Novel_Strand_Specific_Amplification_Analysis","translated_internal_url":"","created_at":"2024-08-14T06:25:46.057-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":106663690,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":117443672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/117443672/thumbnails/1.jpg","file_name":"4798.pdf","download_url":"https://www.academia.edu/attachments/117443672/download_file?st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&st=MTczMzM0ODY4Niw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Determination_of_the_Ex_Vivo_Rates_of_Hu.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/117443672/4798-libre.pdf?1723642535=\u0026response-content-disposition=attachment%3B+filename%3DDetermination_of_the_Ex_Vivo_Rates_of_Hu.pdf\u0026Expires=1733352286\u0026Signature=X~6LtB-0N56bnM011UNhaC2fFq0w5tj~v~w9dXie173ezNnnKbWBvINc2v1G66QJawvdSCkzjzcgcgqysRH9JF7Gk8hzHM-iNDUYuQ89fLwjyE2ssah4zhT8pNTKG2IZ~vmSLLJVyfjp-1yD1qGzKyZDes~zT-eLhvEbtw14AAoMfPh3RUKqUsDzYzmRlY-ghzKl1DJSpcGLS6koCIjLiUsMuROv7IQ269AOcItGF77UkAaEpfi9zLkXXn6ec--H2Qzc22srN7WjYbcRw-v3w2to7aQaskYvddgRNZwww4AdJqtg1KzGZ-GipLrnTYWNJwem~VjSm~ZoHzZPFbjltQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Determination_of_the_Ex_Vivo_Rates_of_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcription_by_Using_Novel_Strand_Specific_Amplification_Analysis","translated_slug":"","page_count":10,"language":"en","content_type":"Work","owner":{"id":106663690,"first_name":"Vinay","middle_initials":null,"last_name":"Pathak","page_name":"VinayPathak","domain_name":"mu","created_at":"2019-03-27T05:08:20.428-07:00","display_name":"Vinay 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="122873284"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/122873284/APOBEC3F_and_APOBEC3G_Inhibit_HIV_1_DNA_Integration_by_Different_Mechanisms"><img alt="Research paper thumbnail of APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/122873284/APOBEC3F_and_APOBEC3G_Inhibit_HIV_1_DNA_Integration_by_Different_Mechanisms">APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms</a></div><div class="wp-workCard_item"><span>Journal of Virology</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit hu...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81:7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. We further investigated the mechanisms by which A3F and A3G block viral DNA integration by analyzing their effects on viral cDNA processing using S...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="122873284"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="122873284"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 122873284; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=122873284]").text(description); $(".js-view-count[data-work-id=122873284]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 122873284; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='122873284']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 122873284, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=122873284]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":122873284,"title":"APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms","translated_title":"","metadata":{"abstract":"APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81:7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. 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