Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation

查看全文 作　　者：Ting [1]Gao;Lin [1,2]Zhu;Hainan [1]Liu;Xiaopeng [1]Zhang;Tingting [2]Wang;Yangbo [1]Fu;Hongzhen [3]Li;Qincai [1]Dong;Yong [1]Hu;Zhang [1]Zhang;Jing [2]Jin;Zijing [1]Liu;Weihong [2]Yang;Yaoning [2]Liu;Yanwen [1]Jin;Kaitong [3]Li;Yongjiu [4]Xiao;Junli [1]Liu;Huailong [1]Zhao;Yue [1]Liu;Ping [1]Li;Jibo [5]Song;Lu [4]Zhang;Yuwei [6]Gao;Sisi [7]Kang;Shoudeng [7]Chen;Qingjun [1]Ma;Xiuwu [8]Bian;Wei [1]Chen;Xuan [1]Liu;Qing [8]Mao;Cheng [1]Cao

机构地区：[1]Institute of Biotechnology,Academy of Military Medical Sciences,Beijing 100850,China;[2]Institute of Physical Science and Information Technology,Anhui University,Hefei,Anhui 230601,China;[3]Beijing Key Laboratory of Bio-products Safety Assessment,Joinn Laboratories(China)Co.Ltd,Beijing 100176,China;[4]The 940th Hospital of the People’s Liberation Army,Lanzhou,Gansu 730050,China;[5]Department of Gastroenterology,the 960th Hospital of the People’s Liberation Army,Zibo,Shandong 255300,China;[6]Academy of Military Medical Science of PLA,666 Liuyingxi St,Changchun 130122,China;[7]Molecular Imaging Center,Guangdong Provincial Key Laboratory of Biomedical Imaging,The Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai 519000,China;[8]First Affiliated Hospital,Army Medical University,Chongqing 400038,China

出　　处：《Signal Transduction and Targeted Therapy》索引2022年第7卷第10期,共15页

基　　金：funded by the National Science and Technology Major Projects(2018ZX09711003-005-005 and 2018ZX09201017-007);the National Basic Research Program of China(2012CB518902). 摘　　要：Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses,but the underlying mechanism remains unclear.In this study,the N proteins of highly pathogenic human coronaviruses,including severe acute respiratory syndrome coronavirus(SARS-CoV),middle east respiratory syndrome coronavirus(MERS-CoV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),were found to bind MASP-2,a key serine protease in the lectin pathway of complement activation,resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation,and the deposition of MASP-2,C4b,activated C3 and C5b-9.Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein.Complement hyperactivation was also observed in SARS-CoV-2-infected patients.Either blocking the N protein:MASP-2 interaction,MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo.Altogether,these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses. 关键词：LUNG INFLAMMATION activation

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Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation

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