tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2020 Dec 28;5(1):299.
doi: 10.1038/s41392-020-00438-7.
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
Yi Zheng[SUP] 1 [/SUP], Meng-Wei Zhuang[SUP] 2 [/SUP], Lulu Han[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Mei-Ling Nan[SUP] 2 [/SUP], Peng Zhan[SUP] 3 4 [/SUP], Dongwei Kang[SUP] 3 4 [/SUP], Xinyong Liu[SUP] 3 4 [/SUP], Chengjiang Gao[SUP] 5 [/SUP], Pei-Hui Wang[SUP] 6 7 [/SUP]
Affiliations
Abstract
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.
. 2020 Dec 28;5(1):299.
doi: 10.1038/s41392-020-00438-7.
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
Yi Zheng[SUP] 1 [/SUP], Meng-Wei Zhuang[SUP] 2 [/SUP], Lulu Han[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Mei-Ling Nan[SUP] 2 [/SUP], Peng Zhan[SUP] 3 4 [/SUP], Dongwei Kang[SUP] 3 4 [/SUP], Xinyong Liu[SUP] 3 4 [/SUP], Chengjiang Gao[SUP] 5 [/SUP], Pei-Hui Wang[SUP] 6 7 [/SUP]
Affiliations
- PMID: 33372174
- DOI: 10.1038/s41392-020-00438-7
Abstract
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.