Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling.
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严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 膜 (M) 蛋白通过靶向 RIG-I/MDA-5 信号传导抑制 I 型和 III 型干扰素产生
DOI：
10.1038/s41392-020-00438-7
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发表时间：
2020-12-28
影响因子：
39.3
通讯作者：
Wang PH
中科院分区：
文献类型：
--
作者：
Zheng Y;Zhuang MW;Han L;Zhang J;Nan ML;Zhan P;Kang D;Liu X;Gao C;Wang PH
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）已在全球范围内迅速蔓延，并影响了1000多万人。COVID-19的一个典型特征是抑制I型和III型干扰素（IFN）介导的抗病毒免疫。然而，SARS-CoV-2逃避抗病毒免疫的分子机制仍然难以捉摸。在这里，我们报道了SARS-CoV-2膜（M）蛋白抑制由RIG-I/MDA-5-MAVS信号传导介导的胞质dsRNA传感途径诱导的I型和III型IFN的产生。此外，SARS-CoV-2 M蛋白抑制由SeV感染或poly（I：C）转染刺激的I型和III型IFN诱导。从机制上讲，SARS-CoV-2 M蛋白与RIG-I、MAVS和TBK 1相互作用，从而阻止含有RIG-I、MAVS、TRAF 3和TBK 1的多蛋白复合物的形成，并随后阻碍IRF 3的磷酸化、核转位和活化。因此，SARS-CoV-2 M蛋白的异位表达促进了水疱性口炎病毒的复制。总之，这些结果表明SARS-CoV-2 M蛋白通过靶向RIG-I/MDA-5信号传导拮抗I型和III型IFN的产生，其随后减弱抗病毒免疫并增强病毒复制。该研究为解释SARS-CoV-2诱导的抗病毒免疫抑制提供了新的见解，并阐明了COVID-19的致病机制。
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread worldwide and has affected more than 10 million individuals. A typical feature of COVID-19 is the suppression of type I and III interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism by which SARS-CoV-2 evades antiviral immunity remains elusive. Here, we reported that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III IFNs induced by the cytosolic dsRNA-sensing pathway mediated by RIG-I/MDA-5–MAVS signaling. In addition, the SARS-CoV-2 M protein suppresses type I and III IFN induction stimulated by SeV infection or poly (I:C) transfection. Mechanistically, the SARS-CoV-2 M protein interacts with RIG-I, MAVS, and TBK1, thus preventing the formation of the multiprotein complex containing RIG-I, MAVS, TRAF3, and TBK1 and subsequently impeding the phosphorylation, nuclear translocation, and activation of IRF3. Consequently, ectopic expression of the SARS-CoV-2 M protein facilitates the replication of vesicular stomatitis virus. Taken together, these results indicate that the SARS-CoV-2 M protein antagonizes type I and III IFN production by targeting RIG-I/MDA-5 signaling, which subsequently attenuates antiviral immunity and enhances viral replication. This study provides insight into the interpretation of SARS-CoV-2-induced antiviral immune suppression and illuminates the pathogenic mechanism of COVID-19.
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影响因子：
32.4
作者：
Ni, Ling;Ye, Fang;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
56.9
作者：
Broggi, Achille;Ghosh, Sreya;Zanoni, Ivan
通讯作者：
Zanoni, Ivan
严重的急性呼吸综合征冠状病毒M蛋白通过阻碍Traf3.tank.tbk1/ikkepsilon Complex的形成，抑制I型干扰素的产生。
DOI：
10.1074/jbc.m109.008227
发表时间：
2009-06-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Siu KL;Kok KH;Ng MJ;Poon VKM;Yuen KY;Zheng BJ;Jin DY
通讯作者：
Jin DY
影响因子：
13.2
作者：
Lui PY;Wong LY;Fung CL;Siu KL;Yeung ML;Yuen KS;Chan CP;Woo PC;Yuen KY;Jin DY
通讯作者：
Jin DY
SARS-CoV-2 激活和逃避 I 型干扰素反应
影响因子：
16.6
作者：
Lei, Xiaobo;Dong, Xiaojing;Wang, Jianwei
通讯作者：
Wang, Jianwei