Identification of DAXX As A Restriction Factor Of SARS-CoV-2 Through A CRISPR/Cas9 Screen
Identification of DAXX As A Restriction Factor Of SARS-CoV-2 Through A CRISPR/Cas9 Screen
Abstract While interferon restricts SARS-CoV-2 replication in cell culture, 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 identified 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 replication in human cells. Basal expression of DAXX was sufficient to limit the replication of the virus, and DAXX over-expression further restricted infection. In contrast with most of its previously described antiviral activities, DAXX-mediated restriction of SARS-CoV-2 was independent of the SUMOylation pathway. SARS-CoV-2 infection triggered the re-localization of DAXX to cytoplasmic sites of viral replication and led to its degradation. Together, these results demonstrate that DAXX is a potent restriction factor for SARS-CoV-2 and that the virus has evolved a mechanism to counteract its action.
Simon-Lori¨¨re Etienne、Maarifi Ghizlane、Arhel Nathalie、Hardy Alexandra、Porrot Fran?oise、OhAinle Molly、Jouvenet Nolwenn、Nisole S¨|bastien、Tran Quang Dinh、Vallet Thomas、Oki Jennifer、Aicher Sophie-Marie、Bruel Timoth¨|e、Roesch Ferdinand、Schwartz Olivier、Holden Kevin、Chazal Maxime、Kain Alice Mac、Baidaliuk Artem、Carlson-Stevermer Jared、Vignuzzi Marco
Evolutionary genomics of RNA viruses, Institut PasteurInstitut de Recherche en Infectiologie de Montpellier (IRIM), Universit¨| de MontpellierInstitut de Recherche en Infectiologie de Montpellier (IRIM), Universit¨| de MontpellierViral populations and pathogenesis, Institut PasteurVirus and Immunity, Institut PasteurDivisions of Human Biology, Fred Hutchinson Cancer Research CenterVirus sensing and signaling, Institut PasteurInstitut de Recherche en Infectiologie de Montpellier (IRIM), Universit¨| de MontpellierViral populations and pathogenesis, Institut Pasteur||Universit¨| de ParisViral populations and pathogenesis, Institut PasteurSynthego CorporationUniversit¨| de Paris||Virus sensing and signaling, Institut PasteurVirus and Immunity, Institut PasteurViral populations and pathogenesis, Institut Pasteur||UMR 1282 ISP, INRAE Centre Val de LoireVirus and Immunity, Institut PasteurSynthego CorporationVirus sensing and signaling, Institut PasteurViral populations and pathogenesis, Institut Pasteur||Universit¨| de ParisEvolutionary genomics of RNA viruses, Institut PasteurSynthego CorporationViral populations and pathogenesis, Institut Pasteur
基础医学分子生物学生物科学研究方法、生物科学研究技术
Simon-Lori¨¨re Etienne,Maarifi Ghizlane,Arhel Nathalie,Hardy Alexandra,Porrot Fran?oise,OhAinle Molly,Jouvenet Nolwenn,Nisole S¨|bastien,Tran Quang Dinh,Vallet Thomas,Oki Jennifer,Aicher Sophie-Marie,Bruel Timoth¨|e,Roesch Ferdinand,Schwartz Olivier,Holden Kevin,Chazal Maxime,Kain Alice Mac,Baidaliuk Artem,Carlson-Stevermer Jared,Vignuzzi Marco.Identification of DAXX As A Restriction Factor Of SARS-CoV-2 Through A CRISPR/Cas9 Screen[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.05.06.442916.点此复制
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