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SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation
Preprint
in En
| PREPRINT-BIORXIV
| ID: ppbiorxiv-476693
ABSTRACT
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 novel mechanism by which the SARS-CoV-2 virus co-opts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-{beta}. We reveal that the SARS-CoV-2 encoded Non-Structural 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-{beta} production, leading to reduced viral infection. Our findings reveal a new target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.
cc_by_nc_nd
Full text:
1
Collection:
09-preprints
Database:
PREPRINT-BIORXIV
Language:
En
Year:
2022
Document type:
Preprint