Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) membrane (M) protein inhibits type I and IIIinterferon production by targeting RIG-I/MDA-5 signaling

作     者：Yi Zheng Meng-Wei Zhuang Lulu Han Jing Zhang Mei-Ling Nan Peng Zhan Dongwei Kang Xinyong Liu Chengjiang Gao Pei-Hui Wang Yi Zheng;Meng-Wei Zhuang;Lulu Han;Jing Zhang;Mei-Ling Nan;Peng Zhan;Dongwei Kang;Xinyong Liu;Chengjiang Gao;Pei-Hui Wang

作者机构：Key Laboratory of Infection and Immunity of Shandong ProvinceDepartment of ImmunologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University250012 JinanChina Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research InstituteCheeloo College of MedicineShandong University250012 JinanChina Department of Medicinal ChemistryKey Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong University44 West Culture Road250012 JinanShandongPR China China–Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province44 West Culture Road250012 JinanShandongPR China Suzhou Research InstituteShandong UniversityShandong UniversitySuzhouJiangsu 215123China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2021年第6卷第1期

页      面：171-183页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：This work was supported by grants from the COVID-19 emergency tackling research project of Shandong University(Grant No.2020XGB03 to P.-H.W) grants from the Natural Science Foundation of Jiangsu Province(SBK2020042706 to P.-H.W) grants from the Natural Science Foundation of China(81930039,31730026,81525012)awarded to C.G the Fundamental Research Funds of Shandong University(21510078614099) the Fundamental Research Funds of Cheeloo College of Medicine(21510089393109) China Postdoctoral Science Foundation(2018M642662) the Natural Science Foundation of China(81901604)awarded to Y.Z grants from the Key Research and Development Project of Shandong Province(2020SFXGFY08) 

主　　题：immunity acute MAVS 

摘      要：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 ***,the molecular mechanism by which SARS-CoV-2 evades antiviral immunity remains ***,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 *** addition,the SARS-CoV-2 M protein suppresses type I and III IFN induction stimulated by SeV infection or poly(I:C)***,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 ***,ectopic expression of the SARS-CoV-2 M protein facilitates the replication of vesicular stomatitis *** 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 *** study provides insight into the interpretation of SARS-CoV-2-induced antiviral immune suppression and illuminates the pathogenic mechanism of COVID-19.