SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation

Jung-Hyun Choi, Xu Zhang, Christine Zhang, David L Dai, Jun Luo, Reese Ladak, Qian Li, Shane Wiebe, Alex C H Liu, Xiaozhuo Ran, Jiaqi Yang, Parisa Naeli, Aitor Garzia, Lele Zhou, Niaz Mahmood, Qiyun Deng, Mohamed Elaish, Rongtuan Lin, Tom Hobman, Jerry PelletierTommy Alain, Silvia Vidal, Thomas Duchaine, Mohammad T Mazhab-Jafari, Xiaojuan Mao, Seyed Mehdi Jafarnejad, Nahum Sonenberg

Research output: Other contribution

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-β. 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-β 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.Competing Interest StatementThe authors have declared no competing interest.
Original languageEnglish
TypeArticle
Media of outputbioRxiv Preprint Server
Publication statusPublished - 20 Jan 2022

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