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.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","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","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.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.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"]]