Authors:
Alice Mac Kain, Alice Mac Kain, Ghizlane Maarifi, Sophie-Marie Aicher, Sophie-Marie Aicher, Nathalie J. Arhel, Artem Baidaliuk, Thomas Vallet, Quang Dinh Tran, Quang Dinh Tran, Alexandra Hardy, Maxime Chazal, Françoise Porrot, Molly OhAinle, Jared C (...)
Alice Mac Kain, Alice Mac Kain, Ghizlane Maarifi, Sophie-Marie Aicher, Sophie-Marie Aicher, Nathalie J. Arhel, Artem Baidaliuk, Thomas Vallet, Quang Dinh Tran, Quang Dinh Tran, Alexandra Hardy, Maxime Chazal, Françoise Porrot, Molly OhAinle, Jared Carlson-Stevermer, Jennifer Oki, Kevin Holden, Etienne Simon-Loriere, Timothée Bruel, Olivier Schwartz, Nolwenn Jouvenet, Sébastien Nisole, Marco Vignuzzi, Ferdinand Roesch
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Abstract:
AbstractInterferon 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 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 and SARS-CoV replication in human cells. Basal expression o (...)
AbstractInterferon 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 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 and SARS-CoV replication in human cells. Basal expression of DAXX was sufficient to limit the replication of SARS-CoV-2, 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 and promoted its degradation. Mechanistically, this process was 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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