Winkler, Michael

[["dc.bibliographiccitation.artnumber","e97695"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Eckert, Nadine"],["dc.contributor.author","Wrensch, Florian"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Palanisamy, Navaneethan"],["dc.contributor.author","Goedecke, Ulrike"],["dc.contributor.author","Jäger, Nils"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Winkler, Michael"],["dc.date.accessioned","2019-07-09T11:39:43Z"],["dc.date.available","2019-07-09T11:39:43Z"],["dc.date.issued","2014"],["dc.description.abstract","Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis. Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase. Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail. Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells. Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1–3, which are known to inhibit influenza virus entry. Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane. In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels."],["dc.identifier.doi","10.1371/journal.pone.0097695"],["dc.identifier.pmid","24842154"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10118"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58030"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Influenza A Virus Encoding Secreted Gaussia Luciferase as Useful Tool to Analyze Viral Replication and Its Inhibition by Antiviral Compounds and Cellular Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3859"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Wrensch, Florian"],["dc.contributor.author","Bosch, Pascale"],["dc.contributor.author","Knoth, Maike"],["dc.contributor.author","Schindler, Michael"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2020-12-10T18:47:09Z"],["dc.date.available","2020-12-10T18:47:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3390/ijms20163859"],["dc.identifier.eissn","1422-0067"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16799"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78659"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Analysis of IFITM-IFITM Interactions by a Flow Cytometry-Based FRET Assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e49630"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Sinigalia, Elisa"],["dc.contributor.author","Alvisi, Gualtiero"],["dc.contributor.author","Segre, Chiara V."],["dc.contributor.author","Mercorelli, Beatrice"],["dc.contributor.author","Muratore, Giulia"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Ripalti, Alessandro"],["dc.contributor.author","Chiocca, Susanna"],["dc.contributor.author","Palu, Giorgio"],["dc.contributor.author","Loregian, Arianna"],["dc.date.accessioned","2018-11-07T09:03:26Z"],["dc.date.available","2018-11-07T09:03:26Z"],["dc.date.issued","2012"],["dc.description.abstract","During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system."],["dc.identifier.doi","10.1371/journal.pone.0049630"],["dc.identifier.isi","000311272300059"],["dc.identifier.pmid","23166733"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9466"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24902"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","The Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Is Modified by SUMO in a DNA-Dependent Manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Virology Journal"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Lambertz, Ruth Lydia Olga"],["dc.contributor.author","Gerhauser, Ingo"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Leist, Sarah Rebecca"],["dc.contributor.author","Kollmus, Heike"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Schughart, Klaus"],["dc.date.accessioned","2020-12-10T18:39:01Z"],["dc.date.available","2020-12-10T18:39:01Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1186/s12985-020-01323-z"],["dc.identifier.eissn","1743-422X"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17233"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77513"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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","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","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"]]

[["dc.bibliographiccitation.artnumber","e0172847"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Wrensch, Florian"],["dc.contributor.author","Krawczak, Michael"],["dc.contributor.author","Sauermann, Ulrike"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2019-07-09T11:43:17Z"],["dc.date.available","2019-07-09T11:43:17Z"],["dc.date.issued","2017"],["dc.description.abstract","nterferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1 001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals."],["dc.identifier.doi","10.1371/journal.pone.0172847"],["dc.identifier.pmid","28257482"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14379"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58850"],["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.title","Rhesus macaque IFITM3 gene polymorphisms and SIV infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","2104.e10"],["dc.bibliographiccitation.firstpage","2092"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Braun, Elisabeth"],["dc.contributor.author","Hotter, Dominik"],["dc.contributor.author","Koepke, Lennart"],["dc.contributor.author","Zech, Fabian"],["dc.contributor.author","Groß, Rüdiger"],["dc.contributor.author","Sparrer, Konstantin M.J."],["dc.contributor.author","Müller, Janis A."],["dc.contributor.author","Pfaller, Christian K."],["dc.contributor.author","Heusinger, Elena"],["dc.contributor.author","Wombacher, Rebecka"],["dc.contributor.author","Sutter, Kathrin"],["dc.contributor.author","Dittmer, Ulf"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Simmons, Graham"],["dc.contributor.author","Jakobsen, Martin R."],["dc.contributor.author","Conzelmann, Karl-Klaus"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Münch, Jan"],["dc.contributor.author","Fackler, Oliver T."],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Sauter, Daniel"],["dc.date.accessioned","2019-07-09T11:51:46Z"],["dc.date.available","2019-07-09T11:51:46Z"],["dc.date.issued","2019"],["dc.description.abstract","Guanylate-binding protein (GBP) 5 is an interferon (IFN)-inducible cellular factor reducing HIV-1 infectivity by an incompletely understood mechanism. Here, we show that this activity is shared by GBP2, but not by other members of the human GBP family. GBP2/5 decrease the activity of the cellular proprotein convertase furin, which mediates conversion of the HIV-1 envelope protein (Env) precursor gp160 into mature gp120 and gp41. Because this process primes HIV-1 Env for membrane fusion, viral particles produced in the presence of GBP2/5 are poorly infectious due to increased incorporation of non-functional gp160. Furin activity is critical for the processing of envelope glycoproteins of many viral pathogens. Consistently, GBP2/5 also inhibit Zika, measles, and influenza A virus replication and decrease infectivity of viral particles carrying glycoproteins of Marburg and murine leukemia viruses. Collectively, our results show that GPB2/5 exert broad antiviral activity by suppressing the activity of the virus-dependency factor furin."],["dc.identifier.doi","10.1016/j.celrep.2019.04.063"],["dc.identifier.pmid","31091448"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16188"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60006"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","599"],["dc.title","Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]