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<!DOCTYPE html> <html lang="en"> <head> <meta charset="utf-8">  <title>Interaction of DCs and viruses - Immunmodulation | Uniklinikum Erlangen</title> <meta http-equiv="x-ua-compatible" content="IE=edge"> <meta name="generator" content="TYPO3 CMS"> <meta name="description" content="Die Projektgruppe ”DZ und Viren” untersucht die Rolle der DZ bei viralen Infektionen, insbesondere HSV-1 und HCMV. Im Rahmen dieser Untersuchungen konnten in den vergangenen Jahren mehrere, Virus-spezifische Immunevasionsmechanismen identifiziert werden. Unter anderem bewirkt HSV-1 im Zuge der Infektion reifer DZ eine spezifische, Proteasom-abhängige Degradation des Oberflächenmoleküls CD83, welches zu einer reduzierten T-Zellaktivierung führt. Der exakte Mechanismus dieser Degradation ist Gegenstand unserer aktuellen Forschung. Darüber hinaus führt die Infektion von reifen DZ mit HCMV zur Abspaltung eines löslichen CD83-Moleküls, welches immunsuppressive Eigenschaften besitzt. Außerdem konnten wir zeigen, dass die Infektion reifer DZ mit HSV-1 über den Verlust des Interferon-? Rezeptors 1 zu einer Hemmung des STAT1-Signalweges führt. In weiteren Untersuchungen beschäftigt sich die Arbeitsgruppe mit der Replikation von HSV-1 in reifen DZ. Entgegen früherer Berichte konnten wir zeigen, dass HSV- 1 sehr wohl in reifen DZ repliziert, allerdings ist diese Replikation sehr ineffizient. Dass dies dennoch von biologischer Bedeutung ist, zeigt die Tatsache, dass die neu entstandenen Viren über Zell-Zell-Kontakt an andere Zellen, auch primäre, weitergegeben werden können. Bei dieser Weitergabe spielt offenbar das virale Glykoprotein gE eine entscheidende Rolle. Ein weiterer Schwerpunkt stellt die HSV-1 Inhibition der DZ-Migration dar, welche ebenfalls zu einer Blockade der T-Zellaktivierung führt."> <meta name="viewport" content="width=device-width, initial-scale=1, minimum-scale=1"> <meta name="robots" content="index,follow"> <meta name="twitter:card" content="summary"> <meta name="apple-mobile-web-app-capable" content="no"> <meta name="google" content="notranslate"> <link rel="stylesheet" href="/_assets/d62557c271d06262fbb7ce0981266e2f/Css/auto-complete.1732120249.css" media="all"> <link rel="stylesheet" href="/_assets/db5fd2ca3057ef07b5244af171451057/Css/ods_osm.1714687028.css" media="all"> <link rel="stylesheet" href="/_frontend/website/bundled/css/default.6c6d42ec.1730828947.css" media="all"> <style> #frame-backgroundimage-14466 { background-image: url('/fileadmin/_processed_/a/c/csm_header_forschung_5143c2da1e.jpg'); } @media (min-width: 768px) { #frame-backgroundimage-14466 { background-image: 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class="frame-header"><h2 class="element-header "><span>Interaction of DCs and viruses</span></h2></div><h3>Project manager: Dr. Alexandra Birzer</h3><p>This research group focuses on the interaction of DCs and specific viruses, including HSV-1/2 and HCMV. To induce potent immune responses against pathogens, e.g. viruses, DCs play a pivotal role. Thus, it is not surprising that many viruses developed specific immune-escape mechanisms, during their coevolution with the host. We are particularly interested to elucidate the molecular mechanisms leading to such immune escape strategies. In this regard we recently reported, that both adhesion and migration of human DCs, are targeted by herpes simplex virus type-1 (HSV-1) and HSV-2. Enhanced DC-adhesion leads to impaired migration of these cells into the draining lymph nodes and subsequently to reduced anti-viral immune responses.</p><p>Moreover, we discovered that HSV-1 specifically modulates the IL-6 signaling pathway in human mDCs. Using phenotypic FACS analyses we showed that IL-6 receptor surface expression was strongly impaired on directly HSV-1-infected mDCs. Surprisingly this was also the case when we analyzed uninfected, bystander mDCs. This is facilitated so-called non-infectious light (L)-particles, which in comparison to infectious heavy (H)-particles, do not contain the viral capsid and thus miss the viral genome. However, they contain many viral proteins, which are sufficient to down-modulate IL-6 receptor expression on mDCs. To obtain further insights, regarding the precise protein composition of these non-infectious L-particles, we performed mass spectrometry analyses, and compared L-particles with infectious H-particles.</p><p>In addition, we are interested in the DC-specific viral replication cycle and compared immature iDCs with mature mDCs, and observed a very interesting difference between these cells.  Surprisingly, only iDCs generate infectious H-particles, while mDCs only facilitate the production of non-infectious L-particles. Mechanistically, we found that in mDCs HSV-1 capsids are trapped within the nucleus, thereby inhibiting the viral replication cycle. In sharp contrast, iDCs facilitate an autophagy dependent degradation of the nuclear lamin layer, and thus induce the completion of the viral replication cycle, leading to the generation of infectious viral particles. This represents a new and very interesting mDC-specific mechanisms, to inhibit viral replication.<br>  </p><p><a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Heilingloh+Christiane" target="_blank" class="link link-external" title="EXT:site/Resources/Private/Language/locallang_rte.xml:external_link_titleText_new_window" rel="noreferrer">Publications</a></p></div></div></div></div></div></div></div><div id="c44531" class=" frame frame-default frame-type-list frame-layout-default frame-size-default frame-height-default frame-background-none frame-space-before-none frame-space-after-none frame-no-backgroundimage"><div class="frame-group-container"><div class="frame-group-inner"><div class="frame-container frame-container-default"><div class="frame-inner"><a id="c44532"></a><div class="frame-header"><h3 class="element-header "><span>Project manager: Dr. Alexandra Birzer</span></h3></div><div class="result-list-items contact-items result-list-items-glossar columnsCount2"><div class="result-list-item"><div class="list-item-text"><div class="category-flag-wrapper"><div class="category-flag"><a title="Opens the website of Immunmodulation" target="_blank" href="/en/">Immunmodulation</a></div></div><h4><a title="opens business card of Philipp Beck M. 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