Xu Z, Choi JH, Dai DL, Luo J, Ladak RJ, Li Q, Wang Y, Zhang C, Wiebe S, Liu ACH, Ran X, Yang J, Naeli P, Garzia A, Zhou L, Mahmood N, Deng Q, Elaish M, Lin R, Mahal LK, Hobman TC, Pelletier J, Alain T, Vidal SM, Duchaine T, Mazhab-Jafari MT, Mao X, Jafarnejad SM, Sonenberg N

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-?. We reveal ...

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that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-? production, which inhibits SARS-CoV-2 replication. Our findings reveal a target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.

Date: Aug. 09, 2022

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