Winkler, Michael

[["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","e0214968"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Plegge, Teresa"],["dc.contributor.author","Spiegel, Martin"],["dc.contributor.author","Krüger, Nadine"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","González Hernández, Mariana"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2019-07-09T11:51:10Z"],["dc.date.available","2019-07-09T11:51:10Z"],["dc.date.issued","2019"],["dc.description.abstract","Emerging viruses such as severe fever and thrombocytopenia syndrome virus (SFTSV) and Ebola virus (EBOV) are responsible for significant morbidity and mortality. Host cell proteases that process the glycoproteins of these viruses are potential targets for antiviral intervention. The aspartyl protease signal peptide peptidase (SPP) has recently been shown to be required for processing of the glycoprotein precursor, Gn/Gc, of Bunyamwera virus and for viral infectivity. Here, we investigated whether SPP is also required for infectivity of particles bearing SFTSV-Gn/Gc. Entry driven by the EBOV glycoprotein (GP) and the Lassa virus glycoprotein (LASV-GPC) depends on the cysteine proteases cathepsin B and L (CatB/CatL) and the serine protease subtilisin/kexin-isozyme 1 (SKI-1), respectively, and was examined in parallel for control purposes. We found that inhibition of SPP and SKI-1 did not interfere with SFTSV Gn + Gc-driven entry but, unexpectedly, blocked entry mediated by EBOV-GP. The inhibition occurred at the stage of proteolytic activation and the SPP inhibitor was found to block CatL/CatB activity. In contrast, the SKI-1 inhibitor did not interfere with CatB/CatL activity but disrupted CatB localization in endo/lysosomes, the site of EBOV-GP processing. These results underline the potential of protease inhibitors for antiviral therapy but also show that previously characterized compounds might exert broader specificity than initially appreciated and might block viral entry via diverse mechanisms."],["dc.identifier.doi","10.1371/journal.pone.0214968"],["dc.identifier.pmid","30973897"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16063"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59889"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","599"],["dc.title","Inhibitors of signal peptide peptidase and subtilisin/kexin-isozyme 1 inhibit Ebola virus glycoprotein-driven cell entry by interfering with activity and cellular localization of endosomal cathepsins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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"]]