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 mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal 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-β 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.
Keywords: 4EHP; GIGYF2; NSP2; SARS-CoV-2; mRNA translation.
【저자키워드】 SARS-CoV-2, 4EHP, GIGYF2, NSP2, mRNA translation., 【초록키워드】 Cytokines, innate immune response, Antiviral, translation, interferons, SARS-CoV-2 virus, cytokine, type I interferon, Protein, mRNA, RNA viruses, type I interferons, target, SARS-CoV-2 replication, mechanism, IFNs, binding, mRNA translation, cellular, Interaction, GIGYF2, NSP2, immunostimulatory, IFN-β, Depletion, IFNB1, ENhance, intrinsic, significantly, inhibit, interact, evade, suppress, the SARS-CoV-2, the SARS-CoV-2 virus, 【제목키워드】 interferon, mRNA translation, impair,