Activation and evasion of type I interferon responses by SARS-CoV-2

作者：Xiaobo Lei, Xiaojing Dong, Ruiyi Ma, Wenjing Wang, Xia Xiao, Zhongqin Tian, Conghui Wang, Ying Wang, Li Li, Lili Ren, Fei Guo, Zhendong Zhao, Zhuo Zhou, Zichun Xiang, Jianwei Wang · 发表于：Nature Communications · 年份：2020 · DOI：10.1038/s41467-020-17665-9 · 被引用次数：1071 · 研究领域：interferon and immune responses、SARS-CoV-2 and COVID-19 Research、Viral Infections and Outbreaks Research

The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.