期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 5, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-020-00438-7
关键词
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资金
- Shandong University [2020XGB03]
- Natural Science Foundation of Jiangsu Province [SBK2020042706]
- Natural Science Foundation of China [81930039, 31730026, 81525012, 81901604]
- Fundamental Research Funds of Shandong University [21510078614099]
- Fundamental Research Funds of Cheeloo College of Medicine [21510089393109]
- China Postdoctoral Science Foundation [2018M642662]
- Key Research and Development Project of Shandong Province [2020SFXGFY08]
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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