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IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro.
Prelli Bozzo, Caterina; Nchioua, Rayhane; Volcic, Meta; Koepke, Lennart; Krüger, Jana; Schütz, Desiree; Heller, Sandra; Stürzel, Christina M; Kmiec, Dorota; Conzelmann, Carina; Müller, Janis; Zech, Fabian; Braun, Elisabeth; Groß, Rüdiger; Wettstein, Lukas; Weil, Tatjana; Weiß, Johanna; Diofano, Federica; Rodríguez Alfonso, Armando A; Wiese, Sebastian; Sauter, Daniel; Münch, Jan; Goffinet, Christine; Catanese, Alberto; Schön, Michael; Boeckers, Tobias M; Stenger, Steffen; Sato, Kei; Just, Steffen; Kleger, Alexander; Sparrer, Konstantin M J; Kirchhoff, Frank.
  • Prelli Bozzo C; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Nchioua R; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Volcic M; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Koepke L; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Krüger J; Department of Internal Medicine I, Ulm University Medical Center, Ulm, Germany.
  • Schütz D; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Heller S; Department of Internal Medicine I, Ulm University Medical Center, Ulm, Germany.
  • Stürzel CM; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Kmiec D; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Conzelmann C; Department of Infectious Diseases, King's College London, London, UK.
  • Müller J; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Zech F; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Braun E; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Groß R; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Wettstein L; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Weil T; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Weiß J; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Diofano F; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Rodríguez Alfonso AA; Department of Internal Medicine II (Cardiology), Ulm University, Ulm, Germany.
  • Wiese S; Core Facility of Functional Peptidomics, Ulm University Medical Center, Ulm, Germany.
  • Sauter D; Core Unit of Mass Spectrometry and Proteomics, Ulm University Medical Center, Ulm, Germany.
  • Münch J; Core Unit of Mass Spectrometry and Proteomics, Ulm University Medical Center, Ulm, Germany.
  • Goffinet C; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Catanese A; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.
  • Schön M; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Boeckers TM; Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Stenger S; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
  • Sato K; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
  • Just S; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
  • Kleger A; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ulm University, Ulm, Germany.
  • Sparrer KMJ; Institute of Medical Microbiology and Hygiene, Ulm University Medical Center, Ulm, Germany.
  • Kirchhoff F; Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nat Commun ; 12(1): 4584, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1387354
ABSTRACT
Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) can restrict viral pathogens, but pro- and anti-viral activities have been reported for coronaviruses. Here, we show that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. However, endogenous IFITM expression supports efficient infection of SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral infection. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. IFITM-derived peptides and targeting antibodies inhibit SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are cofactors for efficient SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and are potential targets for therapeutic approaches.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antigens, Differentiation / RNA-Binding Proteins / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / Membrane Proteins Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-24817-Y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antigens, Differentiation / RNA-Binding Proteins / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / Membrane Proteins Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-24817-Y