Activation and evasion of type I interferon responses by SARS-CoV-2
Activation and evasion of type I interferon responses by SARS-CoV-2
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SARS-CoV-2 激活和逃避 I 型干扰素反应
DOI：
10.1038/s41467-020-17665-9
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发表时间：
2020-07-30
影响因子：
16.6
通讯作者：
Wang, Jianwei
中科院分区：
文献类型：
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作者：
Lei, Xiaobo;Dong, Xiaojing;Wang, Jianwei
COVID-19疫情对全球公共卫生构成前所未有的威胁。然而，人们对COVID-19病毒病原体SARS-CoV-2和宿主先天免疫之间的相互作用知之甚少。在这里，我们表明，SARS-CoV-2诱导明显的，但延迟的I型干扰素（IFN）的反应。通过对23种病毒蛋白的筛选，我们发现SARS-CoV-2 NSP 1、NSP 3、NSP 12、NSP 13、NSP 14、ORF 3、ORF 6和M蛋白抑制仙台病毒诱导的IFN-β启动子激活，而NSP 2和S蛋白则发挥相反的作用。进一步的分析表明，ORF 6抑制I型IFN的产生和下游信号传导，并且ORF 6的C-末端区域对其拮抗作用至关重要。最后，我们发现IFN-β治疗有效地阻断了SARS-CoV-2的复制。总之，我们的研究表明，SARS-CoV-2通过其结构和非结构蛋白干扰宿主的先天免疫反应，从而为SARS-CoV-2的发病机制提供了见解。
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.