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Publication . Preprint . 2021

Identification of DAXX As A Restriction Factor Of SARS-CoV-2 Through A CRISPR/Cas9 Screen

Alice Mac Kain; Ghizlane Maarifi; Sophie-Marie Aicher; Nathalie J. Arhel; Artem Baidaliuk; Thomas Vallet; Quang Dinh Tran; +14 Authors
Open Access
Published: 25 Nov 2021
Publisher: HAL CCSD
Country: France

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.

Subjects by Vocabulary

Medical Subject Headings: viruses skin and connective tissue diseases fungi body regions virus diseases

Microsoft Academic Graph classification: Viral replication Sumoylation Pathway Virology Interferon medicine.drug medicine CRISPR Biology DNA replication Cas9 Virus Death-associated protein 6


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