Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen - Université de Tours Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2022

Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen

Timothée Bruel
Olivier Schwartz

Résumé

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 relocalization 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.
Fichier principal
Vignette du fichier
indentification of DAXX.pdf (5.14 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

pasteur-03707111 , version 1 (25-11-2021)
pasteur-03707111 , version 2 (28-06-2022)

Licence

Paternité

Identifiants

Citer

Alice Mac Kain, Ghizlane Maarifi, Sophie-Marie Aicher, Nathalie Arhel, Artem Baidaliuk, et al.. Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen. Nature Communications, 2022, 13, 13 p. ⟨10.1038/s41467-022-30134-9⟩. ⟨pasteur-03707111v2⟩
90 Consultations
73 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More