Pöhlmann, Stefan

[["dc.bibliographiccitation.artnumber","S2211124721008287"],["dc.bibliographiccitation.firstpage","109415"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Krüger, Nadine"],["dc.contributor.author","Kempf, Amy"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Graichen, Luise"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Sidarovich, Anzhalika"],["dc.contributor.author","Moldenhauer, Anna-Sophie"],["dc.contributor.author","Winkler, Martin S."],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2021-09-01T06:42:36Z"],["dc.date.available","2021-09-01T06:42:36Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1016/j.celrep.2021.109415"],["dc.identifier.pii","S2211124721008287"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89097"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation.issn","2211-1247"],["dc.title","SARS-CoV-2 variant B.1.617 is resistant to bamlanivimab and evades antibodies induced by infection and vaccination"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","930975"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Schlör, Anja"],["dc.contributor.author","Hirschberg, Stefan"],["dc.contributor.author","Amor, Ghada Ben"],["dc.contributor.author","Meister, Toni Luise"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Pfaender, Stephanie"],["dc.contributor.author","Eddin, Omar Kamal"],["dc.contributor.author","Kamhieh-Milz, Julian"],["dc.contributor.author","Hanack, Katja"],["dc.date.accessioned","2022-11-01T10:17:18Z"],["dc.date.available","2022-11-01T10:17:18Z"],["dc.date.issued","2022"],["dc.description.abstract","The ongoing COVID-19 pandemic situation caused by SARS-CoV-2 and variants of concern such as B.1.617.2 (Delta) and recently, B.1.1.529 (Omicron) is posing multiple challenges to humanity. The rapid evolution of the virus requires adaptation of diagnostic and therapeutic applications."],["dc.identifier.doi","10.3389/fimmu.2022.930975"],["dc.identifier.pmid","36189209"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116779"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","SARS-CoV-2 neutralizing camelid heavy-chain-only antibodies as powerful tools for diagnostic and therapeutic applications"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0265453"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Sidarovich, Anzhalika"],["dc.contributor.author","Graichen, Luise"],["dc.contributor.author","Hörnich, Bojan"],["dc.contributor.author","Hahn, Alexander"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.editor","Bogyo, Matthew"],["dc.date.accessioned","2022-04-01T10:02:01Z"],["dc.date.available","2022-04-01T10:02:01Z"],["dc.date.issued","2022"],["dc.description.abstract","Several SARS-CoV-2 variants emerged that harbor mutations in the surface unit of the viral spike (S) protein that enhance infectivity and transmissibility. Here, we analyzed whether ten naturally-occurring mutations found within the extended loop harboring the S1/S2 cleavage site of the S protein, a determinant of SARS-CoV-2 cell tropism and pathogenicity, impact S protein processing and function. None of the mutations increased but several decreased S protein cleavage at the S1/S2 site, including S686G and P681H, the latter of which is found in variants of concern B.1.1.7 (Alpha variant) and B.1.1.529 (Omicron variant). None of the mutations reduced ACE2 binding and cell-cell fusion although several modulated the efficiency of host cell entry. The effects of mutation S686G on viral entry were cell-type dependent and could be linked to the availability of cathepsin L for S protein activation. These results show that polymorphisms at the S1/S2 site can modulate S protein processing and host cell entry."],["dc.identifier.doi","10.1371/journal.pone.0265453"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105803"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1932-6203"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Functional analysis of polymorphisms at the S1/S2 site of SARS-CoV-2 spike protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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.journal","The Lancet Infectious Diseases"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Kempf, Amy"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Schulz, Sebastian R"],["dc.contributor.author","Jäck, Hans-Martin"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Hoffmann, Markus"],["dc.date.accessioned","2022-12-01T08:30:45Z"],["dc.date.available","2022-12-01T08:30:45Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/S1473-3099(22)00733-2"],["dc.identifier.pii","S1473309922007332"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117970"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.issn","1473-3099"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Omicron sublineage BQ.1.1 resistance to monoclonal antibodies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1665"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","The Lancet Infectious Diseases"],["dc.bibliographiccitation.lastpage","1666"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Zhang, Lu"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Kempf, Amy"],["dc.contributor.author","Cossmann, Anne"],["dc.contributor.author","Dopfer-Jablonka, Alexandra"],["dc.contributor.author","Schulz, Sebastian R"],["dc.contributor.author","Jäck, Hans-Martin"],["dc.contributor.author","Behrens, Georg M N"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Hoffmann, Markus"],["dc.date.accessioned","2022-12-01T08:30:45Z"],["dc.date.available","2022-12-01T08:30:45Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/S1473-3099(22)00693-4"],["dc.identifier.pii","S1473309922006934"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117969"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.issn","1473-3099"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","The effect of cilgavimab and neutralisation by vaccine-induced antibodies in emerging SARS-CoV-2 BA.4 and BA.5 sublineages"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Clinical and Translational Medicine"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Hoffmann, Markus"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.date.accessioned","2022-06-01T09:40:13Z"],["dc.date.available","2022-06-01T09:40:13Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1002/ctm2.839"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108670"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","2001-1326"],["dc.relation.issn","2001-1326"],["dc.title","Understanding Omicron: Transmissibility, immune evasion and antiviral intervention"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cellular & Molecular Immunology"],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Kempf, Amy"],["dc.contributor.author","Nehlmeier, Inga"],["dc.contributor.author","Graichen, Luise"],["dc.contributor.author","Winkler, Martin S."],["dc.contributor.author","Lier, Martin"],["dc.contributor.author","Schulz, Sebastian"],["dc.contributor.author","Jäck, Hans-Martin"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Hoffmann, Markus"],["dc.date.accessioned","2022-02-01T10:31:08Z"],["dc.date.available","2022-02-01T10:31:08Z"],["dc.date.issued","2022"],["dc.description.abstract","Since the beginning of the COVID-19 pandemic, multiple SARS-CoV-2 variants have emerged. While some variants spread only locally, others, referred to as variants of concern, disseminated globally and became drivers of the pandemic. All SARS-CoV-2 variants harbor mutations relative to the virus circulating early in the pandemic, and mutations in the viral spike (S) protein are considered of particular relevance since the S protein mediates host cell entry and constitutes the key target of the neutralizing antibody response. As a consequence, mutations in the S protein may increase SARS-CoV-2 infectivity and enable its evasion of neutralizing antibodies. Furthermore, mutations in the S protein can modulate viral transmissibility and pathogenicity."],["dc.description.abstract","Since the beginning of the COVID-19 pandemic, multiple SARS-CoV-2 variants have emerged. While some variants spread only locally, others, referred to as variants of concern, disseminated globally and became drivers of the pandemic. All SARS-CoV-2 variants harbor mutations relative to the virus circulating early in the pandemic, and mutations in the viral spike (S) protein are considered of particular relevance since the S protein mediates host cell entry and constitutes the key target of the neutralizing antibody response. As a consequence, mutations in the S protein may increase SARS-CoV-2 infectivity and enable its evasion of neutralizing antibodies. Furthermore, mutations in the S protein can modulate viral transmissibility and pathogenicity."],["dc.identifier.doi","10.1038/s41423-021-00811-8"],["dc.identifier.pii","811"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98791"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.relation.eissn","2042-0226"],["dc.relation.issn","1672-7681"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","No evidence for increased cell entry or antibody evasion by Delta sublineage AY.4.2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","91"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Biology"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Hein, Marc D."],["dc.contributor.author","Arora, Prerna"],["dc.contributor.author","Marichal-Gallardo, Pavel"],["dc.contributor.author","Winkler, Michael"],["dc.contributor.author","Genzel, Yvonne"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Schughart, Klaus"],["dc.contributor.author","Kupke, Sascha Y."],["dc.contributor.author","Reichl, Udo"],["dc.date.accessioned","2021-07-05T15:00:38Z"],["dc.date.available","2021-07-05T15:00:38Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Background Infections with influenza A virus (IAV) cause high morbidity and mortality in humans. Additional to vaccination, antiviral drugs are a treatment option. Besides FDA-approved drugs such as oseltamivir or zanamivir, virus-derived defective interfering (DI) particles (DIPs) are considered promising new agents. IAV DIPs typically contain a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Consequently, DIPs miss the genetic information necessary for replication and can usually only propagate by co-infection with infectious standard virus (STV), compensating for their defect. In such a co-infection scenario, DIPs interfere with and suppress STV replication, which constitutes their antiviral potential. Results In the present study, we generated a genetically engineered MDCK suspension cell line for production of a purely clonal DIP preparation that has a large deletion in its segment 1 (DI244) and is not contaminated with infectious STV as egg-derived material. First, the impact of the multiplicity of DIP (MODIP) per cell on DI244 yield was investigated in batch cultivations in shake flasks. Here, the highest interfering efficacy was observed for material produced at a MODIP of 1E − 2 using an in vitro interference assay. Results of RT-PCR suggested that DI244 material produced was hardly contaminated with other defective particles. Next, the process was successfully transferred to a stirred tank bioreactor (500 mL working volume) with a yield of 6.0E+8 PFU/mL determined in genetically modified adherent MDCK cells. The produced material was purified and concentrated about 40-fold by membrane-based steric exclusion chromatography (SXC). The DI244 yield was 92.3% with a host cell DNA clearance of 97.1% (99.95% with nuclease digestion prior to SXC) and a total protein reduction of 97.2%. Finally, the DIP material was tested in animal experiments in D2(B6).A2G- Mx1 r/r mice. Mice infected with a lethal dose of IAV and treated with DIP material showed a reduced body weight loss and all animals survived. Conclusion In summary, experiments not only demonstrated that purely clonal influenza virus DIP preparations can be obtained with high titers from animal cell cultures but confirmed the potential of cell culture-derived DIPs as an antiviral agent."],["dc.description.abstract","Abstract Background Infections with influenza A virus (IAV) cause high morbidity and mortality in humans. Additional to vaccination, antiviral drugs are a treatment option. Besides FDA-approved drugs such as oseltamivir or zanamivir, virus-derived defective interfering (DI) particles (DIPs) are considered promising new agents. IAV DIPs typically contain a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Consequently, DIPs miss the genetic information necessary for replication and can usually only propagate by co-infection with infectious standard virus (STV), compensating for their defect. In such a co-infection scenario, DIPs interfere with and suppress STV replication, which constitutes their antiviral potential. Results In the present study, we generated a genetically engineered MDCK suspension cell line for production of a purely clonal DIP preparation that has a large deletion in its segment 1 (DI244) and is not contaminated with infectious STV as egg-derived material. First, the impact of the multiplicity of DIP (MODIP) per cell on DI244 yield was investigated in batch cultivations in shake flasks. Here, the highest interfering efficacy was observed for material produced at a MODIP of 1E − 2 using an in vitro interference assay. Results of RT-PCR suggested that DI244 material produced was hardly contaminated with other defective particles. Next, the process was successfully transferred to a stirred tank bioreactor (500 mL working volume) with a yield of 6.0E+8 PFU/mL determined in genetically modified adherent MDCK cells. The produced material was purified and concentrated about 40-fold by membrane-based steric exclusion chromatography (SXC). The DI244 yield was 92.3% with a host cell DNA clearance of 97.1% (99.95% with nuclease digestion prior to SXC) and a total protein reduction of 97.2%. Finally, the DIP material was tested in animal experiments in D2(B6).A2G- Mx1 r/r mice. Mice infected with a lethal dose of IAV and treated with DIP material showed a reduced body weight loss and all animals survived. Conclusion In summary, experiments not only demonstrated that purely clonal influenza virus DIP preparations can be obtained with high titers from animal cell cultures but confirmed the potential of cell culture-derived DIPs as an antiviral agent."],["dc.identifier.doi","10.1186/s12915-021-01020-5"],["dc.identifier.pii","1020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87872"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.eissn","1741-7007"],["dc.title","Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]