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Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen.
Mac Kain, Alice; Maarifi, Ghizlane; Aicher, Sophie-Marie; Arhel, Nathalie; Baidaliuk, Artem; Munier, Sandie; Donati, Flora; Vallet, Thomas; Tran, Quang Dinh; Hardy, Alexandra; Chazal, Maxime; Porrot, Françoise; OhAinle, Molly; Carlson-Stevermer, Jared; Oki, Jennifer; Holden, Kevin; Zimmer, Gert; Simon-Lorière, Etienne; Bruel, Timothée; Schwartz, Olivier; van der Werf, Sylvie; Jouvenet, Nolwenn; Nisole, Sébastien; Vignuzzi, Marco; Roesch, Ferdinand.
  • Mac Kain A; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Viral populations and pathogenesis Unit, F-75015, Paris, France.
  • Maarifi G; Institut de Recherche en Infectiologie de Montpellier (IRIM), , Université de Montpellier, CNRS, 34090, Montpellier, France.
  • Aicher SM; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Virus sensing and signaling Unit, F-75015, Paris, France.
  • Arhel N; Institut de Recherche en Infectiologie de Montpellier (IRIM), , Université de Montpellier, CNRS, 34090, Montpellier, France.
  • Baidaliuk A; Institut Pasteur, G5 Evolutionary genomics of RNA viruses, F-75015, Paris, France.
  • Munier S; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, F-75015, Paris, France.
  • Donati F; Institut Pasteur, CNR Virus des infections respiratoires, F-75015, Paris, France.
  • Vallet T; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, F-75015, Paris, France.
  • Tran QD; Institut Pasteur, CNR Virus des infections respiratoires, F-75015, Paris, France.
  • Hardy A; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Viral populations and pathogenesis Unit, F-75015, Paris, France.
  • Chazal M; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Viral populations and pathogenesis Unit, F-75015, Paris, France.
  • Porrot F; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Viral populations and pathogenesis Unit, F-75015, Paris, France.
  • OhAinle M; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Virus sensing and signaling Unit, F-75015, Paris, France.
  • Carlson-Stevermer J; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Virus and Immunity, F-75015, Paris, France.
  • Oki J; Divisions of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Holden K; Synthego Corporation, 3565 Haven Avenue, Menlo Park, CA, 94025, USA.
  • Zimmer G; Synthego Corporation, 3565 Haven Avenue, Menlo Park, CA, 94025, USA.
  • Simon-Lorière E; Synthego Corporation, 3565 Haven Avenue, Menlo Park, CA, 94025, USA.
  • Bruel T; Institute of Virology and Immunology, Bern & Mittelhäusern, Switzerland, and Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Schwartz O; Institut Pasteur, G5 Evolutionary genomics of RNA viruses, F-75015, Paris, France.
  • van der Werf S; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Virus and Immunity, F-75015, Paris, France.
  • Jouvenet N; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Virus and Immunity, F-75015, Paris, France.
  • Nisole S; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, F-75015, Paris, France.
  • Vignuzzi M; Institut Pasteur, CNR Virus des infections respiratoires, F-75015, Paris, France.
  • Roesch F; Institut Pasteur, Université de Paris Cité, CNRS UMR 3569, Virus sensing and signaling Unit, F-75015, Paris, France. nolwenn.jouvenet@pasteur.fr.
Nat Commun ; 13(1): 2442, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1890176
ABSTRACT
Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identify DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX is sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricts infection. DAXX restricts an early, post-entry step of the SARS-CoV-2 life cycle. DAXX-mediated restriction of SARS-CoV-2 is independent of the SUMOylation pathway but dependent on its D/E domain, also necessary for its protein-folding activity. SARS-CoV-2 infection triggers the re-localization of DAXX to cytoplasmic sites and promotes its degradation. Mechanistically, this process is mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-30134-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-30134-9