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

作　　者：Ting Gao Lin Zhu Hainan Liu Xiaopeng Zhang Tingting Wang Yangbo Fu Hongzhen Li Qincai Dong Yong Hu Zhang Zhang Jing Jin Zijing Liu Weihong Yang Yaoning Liu Yanwen Jin Kaitong Li Yongjiu Xiao Junli Liu Huailong Zhao Yue Liu Ping Li Jibo Song Lu Zhang Yuwei Gao Sisi Kang Shoudeng Chen Qingjun Ma Xiuwu Bian Wei Chen Xuan Liu Qing Mao Cheng 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》2022年第10期3940-3954,共15页信号转导与靶向治疗（英文）

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 

分 类 号：R37[医药卫生—病原生物学]