Winkler, Michael

[["dc.bibliographiccitation.firstpage","13863"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","13873"],["dc.bibliographiccitation.volume","293"],["dc.contributor.author","Zmora, Pawel"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Kollmus, Heike"],["dc.contributor.author","Moldenhauer, Anna-Sophie"],["dc.contributor.author","Danov, Olga"],["dc.contributor.author","Braun, Armin"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Schughart, Klaus"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2020-12-10T18:12:58Z"],["dc.date.available","2020-12-10T18:12:58Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1074/jbc.RA118.001273"],["dc.identifier.eissn","1083-351X"],["dc.identifier.issn","0021-9258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74544"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0224082"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Markus, Lara"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Krawczak, Michael"],["dc.contributor.author","Sauermann, Ulrike"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2019-11-05T08:51:28Z"],["dc.date.accessioned","2021-10-27T13:13:08Z"],["dc.date.available","2019-11-05T08:51:28Z"],["dc.date.available","2021-10-27T13:13:08Z"],["dc.date.issued","2019"],["dc.description.abstract","The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques."],["dc.identifier.doi","10.1371/journal.pone.0224082"],["dc.identifier.pmid","31682595"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16596"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91754"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1932-6203"],["dc.relation.issn","1932-6203"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","599"],["dc.title","Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["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","e0212757"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PlOS ONE"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Bdeir, Najat"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Reichl, Udo"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Winkler, Michael"],["dc.date.accessioned","2019-07-09T11:50:20Z"],["dc.date.available","2019-07-09T11:50:20Z"],["dc.date.issued","2019"],["dc.description.abstract","Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy."],["dc.identifier.doi","10.1371/journal.pone.0212757"],["dc.identifier.pmid","30822349"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15912"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59749"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","599"],["dc.title","A system for production of defective interfering particles in the absence of infectious influenza A virus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","103255"],["dc.bibliographiccitation.journal","EBioMedicine"],["dc.bibliographiccitation.volume","65"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Smith, Joan C."],["dc.contributor.author","Krüger, Nadine"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Sørensen, Lambert K."],["dc.contributor.author","Søgaard, Ole S."],["dc.contributor.author","Hasselstrøm, Jørgen Bo"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Hempel, Tim"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2022-10-06T13:33:05Z"],["dc.date.available","2022-10-06T13:33:05Z"],["dc.date.issued","2021"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/100010663 ERC"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100004937 Bundesministerium fur Bildung und Forschung Dienststelle Berlin"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1016/j.ebiom.2021.103255"],["dc.identifier.pii","S2352396421000487"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/115541"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.issn","2352-3964"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0179177"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PloS one"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Reinke, Lennart Michel"],["dc.contributor.author","Spiegel, Martin"],["dc.contributor.author","Plegge, Teresa"],["dc.contributor.author","Hartleib, Anika"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Gierer, Stefanie"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2019-07-09T11:43:31Z"],["dc.date.available","2019-07-09T11:43:31Z"],["dc.date.issued","2017"],["dc.description.abstract","The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated."],["dc.identifier.doi","10.1371/journal.pone.0179177"],["dc.identifier.pmid","28636671"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14554"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58903"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","599"],["dc.title","Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e00403-18"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of Virology"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","González-Hernández, Mariana"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Brinkmann, Constantin"],["dc.contributor.author","Nehls, Julia"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Schindler, Michael"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.editor","Dermody, Terence S."],["dc.date.accessioned","2022-10-06T13:25:33Z"],["dc.date.available","2022-10-06T13:25:33Z"],["dc.date.issued","2018"],["dc.description.abstract","ABSTRACT\n The interferon-induced antiviral host cell protein tetherin can inhibit the release of several enveloped viruses from infected cells. The Ebola virus (EBOV) glycoprotein (GP) antagonizes tetherin, but the domains and amino acids in GP that are required for tetherin antagonism have not been fully defined. A GXXXA motif within the transmembrane domain (TMD) of EBOV-GP was previously shown to be important for GP-mediated cellular detachment. Here, we investigated whether this motif also contributes to tetherin antagonism. Mutation of the GXXXA motif did not impact GP expression or particle incorporation and only modestly reduced EBOV-GP-driven entry. In contrast, the GXXXA motif was required for tetherin antagonism in transfected cells. Moreover, alteration of the GXXXA motif increased tetherin sensitivity of a replication-competent vesicular stomatitis virus (VSV) chimera encoding EBOV-GP. Although these results await confirmation with authentic EBOV, they indicate that a GXXXA motif in the TMD of EBOV-GP is important for tetherin antagonism. Moreover, they provide the first evidence that GP can antagonize tetherin in the context of an infectious EBOV surrogate.\n \n IMPORTANCE\n The glycoprotein (GP) of Ebola virus (EBOV) inhibits the antiviral host cell protein tetherin and may promote viral spread in tetherin-positive cells. However, tetherin antagonism by GP has so far been demonstrated only with virus-like particles, and it is unknown whether GP can block tetherin in infected cells. Moreover, a mutation in GP that selectively abrogates tetherin antagonism is unknown. Here, we show that a GXXXA motif in the transmembrane domain of EBOV-GP, which was previously reported to be required for GP-mediated cell rounding, is also important for tetherin counteraction. Moreover, analysis of this mutation in the context of vesicular stomatitis virus chimeras encoding EBOV-GP revealed that GP-mediated tetherin counteraction is operative in infected cells. To our knowledge, these findings demonstrate for the first time that GP can antagonize tetherin in infected cells and provide a tool to study the impact of GP-dependent tetherin counteraction on EBOV spread."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Deutscher Akademischer Austauschdienst https://doi.org/10.13039/501100001655"],["dc.identifier.doi","10.1128/JVI.00403-18"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114864"],["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","A GXXXA Motif in the Transmembrane Domain of the Ebola Virus Glycoprotein Is Required for Tetherin Antagonism"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S210"],["dc.bibliographiccitation.issue","suppl 2"],["dc.bibliographiccitation.journal","Journal of Infectious Diseases"],["dc.bibliographiccitation.lastpage","S218"],["dc.bibliographiccitation.volume","212"],["dc.contributor.author","Wrensch, Florian"],["dc.contributor.author","Karsten, Christina B."],["dc.contributor.author","Gnirß, Kerstin"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Lu, Kai"],["dc.contributor.author","Takada, Ayato"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Simmons, Graham"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2022-10-06T13:35:09Z"],["dc.date.available","2022-10-06T13:35:09Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.1093/infdis/jiv255"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116027"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1537-6613"],["dc.relation.issn","0022-1899"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.title","Interferon-Induced Transmembrane Protein–Mediated Inhibition of Host Cell Entry of Ebolaviruses"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0189073"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.lastpage","19"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Brinkmann, Constantin"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Lübke, Anastasia"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Krämer-Kühl, Annika"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2018-11-16T10:48:50Z"],["dc.date.accessioned","2021-10-27T13:13:15Z"],["dc.date.available","2018-11-16T10:48:50Z"],["dc.date.available","2021-10-27T13:13:15Z"],["dc.date.issued","2017"],["dc.description.abstract","Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread."],["dc.identifier.doi","10.1371/journal.pone.0189073"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15673"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91764"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","1932-6203"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]