SARS-CoV-2 nsp12 attenuates type I interferon production by inhibiting IRF3 nuclear translocation

作者：Wenjing Wang, Zhuo Zhou, Xia Xiao, Zhongqin Tian, Xiaojing Dong, Conghui Wang, Li Li, Lili Ren, Xiaobo Lei, Zichun Xiang, Jianwei Wang · 发表于：Cellular and Molecular Immunology · 年份：2021 · DOI：10.1038/s41423-020-00619-y · 被引用次数：147 · 研究领域：interferon and immune responses、RNA regulation and disease、Viral Infections and Immunology Research

SARS-CoV-2 is the pathogenic agent of COVID-19, which has evolved into a global pandemic. Compared with some other respiratory RNA viruses, SARS-CoV-2 is a poor inducer of type I interferon (IFN). Here, we report that SARS-CoV-2 nsp12, the viral RNA-dependent RNA polymerase (RdRp), suppresses host antiviral responses. SARS-CoV-2 nsp12 attenuated Sendai virus (SeV)- or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner. It also inhibited IFN promoter activation triggered by RIG-I, MDA5, MAVS, and IRF3 overexpression. Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3. Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12. Given these findings, our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.