Winkler, Michael

[["dc.bibliographiccitation.artnumber","e01488-16"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Virology"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Wrensch, Florian"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.editor","Ross, Susan R."],["dc.date.accessioned","2022-10-06T13:25:35Z"],["dc.date.available","2022-10-06T13:25:35Z"],["dc.date.issued","2017"],["dc.description.abstract","ABSTRACT\n Interferon-induced transmembrane proteins (IFITMs) can inhibit the cellular entry of several enveloped viruses, including simian immunodeficiency virus (SIV). The blockade of SIV by IFITMs is isolate specific, raising the question of which parameters impact sensitivity to IFITM. We show that the virion context in which SIV-Env is presented and the efficiency of virion incorporation determine Env susceptibility to inhibition by IFITMs. Thus, determinants other than the nature of the envelope protein can impact the IFITM sensitivity of viral entry.\n \n IMPORTANCE\n The host cell-encoded IFITM proteins can block viral entry and are an important component of the innate defenses against viral infection. However, the determinants controlling whether a virus is susceptible to blockade by IFITM proteins are incompletely understood. Our study shows that the amount of envelope proteins incorporated into virions as well as the nature of the virion particle itself can impact the sensitivity of viral entry to IFITMs. These results show for the first time that determinants other than the viral envelope protein can impact sensitivity to IFITM and have implications for the interpretation of previously published data on inhibition of viruses by IFITM proteins. Moreover, our findings might help to define the mechanism underlying the antiviral activity of IFITM proteins."],["dc.description.sponsorship"," Leibniz-Gemeinschaft https://doi.org/10.13039/501100001664"],["dc.identifier.doi","10.1128/JVI.01488-16"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114874"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1098-5514"],["dc.relation.issn","0022-538X"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e00013-18"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Virology"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","Maschkowitz, Gregor"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Fickenscher, Helmut"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.editor","Sandri-Goldin, Rozanne M."],["dc.date.accessioned","2022-10-06T13:25:31Z"],["dc.date.available","2022-10-06T13:25:31Z"],["dc.date.issued","2018"],["dc.description.abstract","ABSTRACT\n \n Human cytomegalovirus (HCMV) is a widespread human pathogen that causes asymptomatic infection in healthy individuals but poses a serious threat to immunocompromised patients. During the late phase of HCMV infection, the viral capsid is transported to the cytoplasmic viral assembly center (cVAC), where it is enclosed by the tegument protein layer and the viral envelope. The cVAC consists of circularly arranged vesicles from the\n trans\n -Golgi and endosomal networks. The HCMV gene UL35 encodes ppUL35 and its shorter form, ppUL35A. We have previously shown that the UL35 gene is involved in HCMV assembly, but it is unknown how UL35 proteins regulate viral assembly. Here we show that sorting nexin 5 (SNX5), a component of the retromer and part of the retrograde transport pathway, interacts with UL35 proteins. Expression of wild-type proteins but not mutants defective in SNX5 binding resulted in the cellular redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR), indicating that UL35 proteins bind and negatively regulate SNX5 to modulate cellular transport pathways. Furthermore, binding of UL35 proteins to SNX5 was required for efficient viral replication and for transport of the most abundant HCMV glycoprotein B (gB; gpUL55) to the cVAC. These results indicate that ppUL35 and ppUL35A control the localization of the essential gB through the regulation of a retrograde transport pathway. Thus, this work is the first to define a molecular interaction between a tegument protein and a vesicular transport factor to regulate glycoprotein localization.\n \n \n IMPORTANCE\n Human cytomegalovirus is ubiquitously present in the healthy population, but reactivation or reinfection can cause serious, life-threatening infections in immunocompromised patients. For completion of its lytic cycle, human cytomegalovirus induces formation of an assembly center where mature virus particles are formed from multiple viral proteins. Viral glycoproteins use separate vesicular pathways for transport to the assembly center, which are incompletely understood. Our research identified a viral structural protein which affects the localization of one of the major glycoproteins. We could link this change in glycoprotein localization to an interaction of the structural protein with a cellular protein involved in regulation of vesicle transport. This increases our understanding of how the virus intersects into cellular regulatory pathways to enhance its own replication."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1128/JVI.00013-18"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114858"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1098-5514"],["dc.relation.issn","0022-538X"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","https://journals.asm.org/non-commercial-tdm-license"],["dc.title","Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A with Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9178"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Journal of Virology"],["dc.bibliographiccitation.lastpage","9188"],["dc.bibliographiccitation.volume","89"],["dc.contributor.author","Gnirß, Kerstin"],["dc.contributor.author","Zmora, Pawel"],["dc.contributor.author","Blazejewska, Paulina"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Lins, Anika"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Moldenhauer, Anna-Sophie"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Wolff, Thorsten"],["dc.contributor.editor","Lyles, D. S."],["dc.date.accessioned","2022-10-06T13:25:33Z"],["dc.date.available","2022-10-06T13:25:33Z"],["dc.date.issued","2015"],["dc.description.abstract","ABSTRACT\n The expression of the antiviral host cell factor tetherin is induced by interferon and can inhibit the release of enveloped viruses from infected cells. The Vpu protein of HIV-1 antagonizes the antiviral activity of tetherin, and tetherin antagonists with Vpu-like activity have been identified in other viruses. In contrast, it is incompletely understood whether tetherin inhibits influenza A virus (FLUAV) release and whether FLUAV encodes tetherin antagonists. Here, we show that release of several laboratory-adapted FLUAV strains and a seasonal FLUAV strain is inhibited by tetherin, while pandemic FLUAV A/Hamburg/4/2009 is resistant. Studies with a virus-like particle system and analysis of reassortant viruses provided evidence that the viral hemagglutinin (HA) is an important determinant of tetherin antagonism but requires the presence of its cognate neuraminidase (NA) to inhibit tetherin. Finally, tetherin antagonism by FLUAV was dependent on the virion context, since retrovirus release from tetherin-positive cells was not rescued, and correlated with an HA- and NA-dependent reduction in tetherin expression. In sum, our study identifies HA and NA proteins of certain pandemic FLUAV as tetherin antagonists, which has important implications for understanding FLUAV pathogenesis.\n \n IMPORTANCE\n Influenza A virus (FLUAV) infection is responsible for substantial global morbidity and mortality, and understanding how the virus evades the immune defenses of the host may uncover novel targets for antiviral intervention. Tetherin is an antiviral effector molecule of the innate immune system which can contribute to control of viral invasion. However, it has been unclear whether FLUAV is inhibited by tetherin and whether these viruses encode tetherin-antagonizing proteins. Our observation that several pandemic FLUAV strains can counteract tetherin via their HA and NA proteins identifies these proteins as novel tetherin antagonists and indicates that HA/NA-dependent inactivation of innate defenses may contribute to the efficient spread of pandemic FLUAV."],["dc.identifier.doi","10.1128/JVI.00615-15"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114866"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1098-5514"],["dc.relation.issn","0022-538X"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","https://journals.asm.org/non-commercial-tdm-license"],["dc.title","Tetherin Sensitivity of Influenza A Viruses Is Strain Specific: Role of Hemagglutinin and Neuraminidase"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","20477"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Bdeir, Najat"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Winkler, Michael"],["dc.date.accessioned","2021-12-01T09:23:45Z"],["dc.date.available","2021-12-01T09:23:45Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity."],["dc.description.abstract","Abstract Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity."],["dc.identifier.doi","10.1038/s41598-021-99691-1"],["dc.identifier.pii","99691"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94746"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","2045-2322"],["dc.title","Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","91"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Viruses"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Rahman Siregar, Abdul"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Götting, Jasper"],["dc.contributor.author","Stegen, Philipp"],["dc.contributor.author","Kaul, Artur"],["dc.contributor.author","Schulz, Thomas F."],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Winkler, Michael"],["dc.date.accessioned","2022-04-01T10:03:19Z"],["dc.date.available","2022-04-01T10:03:19Z"],["dc.date.issued","2022"],["dc.description.abstract","Primate simplex viruses, including Herpes simplex viruses 1 and 2, form a group of closely related herpesviruses, which establish latent infections in neurons of their respective host species. While neuropathogenic infections in their natural hosts are rare, zoonotic transmission of Macacine alphaherpesvirus 1 (McHV1) from macaques to humans is associated with severe disease. Human infections with baboon-derived Papiine alphaherpesvirus 2 (PaHV2) have not been reported, although PaHV2 and McHV1 share several biological properties, including neuropathogenicity in mice. The reasons for potential differences in PaHV2 and McHV1 pathogenicity are presently not understood, and answering these questions will require mutagenic analysis. Here, we report the development of a recombinant system, which allows rescue of recombinant PaHV2. In addition, we used recombineering to generate viruses carrying reporter genes (Gaussia luciferase or enhanced green fluorescent protein), which replicate with similar efficiency as wild-type PaHV2. We demonstrate that these viruses can be used to analyze susceptibility of cells to infection and inhibition of infection by neutralizing antibodies and antiviral compounds. In summary, we created a recombinant system for PaHV2, which in the future will be invaluable for molecular analyses of neuropathogenicity of PaHV2."],["dc.identifier.doi","10.3390/v14010091"],["dc.identifier.pii","v14010091"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106141"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1999-4915"],["dc.title","A Recombinant System and Reporter Viruses for Papiine Alphaherpesvirus 2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]