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; ... (2022). Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen. Nature Communications, 13(1), p. 2442. Springer Nature 10.1038/s41467-022-30134-9

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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.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology

UniBE Contributor:

Zimmer, Gert


600 Technology > 630 Agriculture




Springer Nature




Pubmed Import

Date Deposited:

06 May 2022 11:46

Last Modified:

05 Dec 2022 16:19

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