HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing.
Fiche publication
Date publication
septembre 2019
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROHR Olivier
Tous les auteurs :
Forouzanfar F, Ali S, Wallet C, De Rovere M, Ducloy C, El Mekdad H, El Maassarani M, Aït-Ammar A, Van Assche J, Boutant E, Daouad F, Margottin-Goguet F, Moog C, Van Lint C, Schwartz C, Rohr O
Lien Pubmed
Résumé
Mammals have evolved many antiviral factors impacting different steps of the viral life cycle. Associated with chromatin-modifying enzymes, the cellular cofactor CTIP2 contributes to HIV-1 gene silencing in latently infected reservoirs that constitute the major block toward an HIV cure. We report, for the first time, that the virus has developed a strategy to overcome this major transcriptional block. Productive HIV-1 infection results in a Vpr-mediated depletion of CTIP2 in microglial cells and CD4+ T cells, two of the major viral reservoirs. Associated to the Cul4A-DDB1-DCAF1 ubiquitin ligase complex, Vpr promotes CTIP2 degradation via the proteasome pathway in the nuclei of target cells and notably at the latent HIV-1 promoter. Importantly, Vpr targets CTIP2 associated with heterochromatin-promoting enzymes dedicated to HIV-1 gene silencing. Thereby, Vpr reactivates HIV-1 expression in a microglial model of HIV-1 latency. Altogether our results suggest that HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing.
Référence
Sci Rep. 2019 Sep 11;9(1):13154