Signal transduction and targeted therapy · 2022
Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gao Ting, Zhu Lin, Liu Hainan, Zhang Xiaopeng, Wang Tingting, Fu Yangbo, Li Hongzhen, Dong Qincai, Hu Yong, Zhang Zhang, Jin Jing, Liu Zijing, Yang Weihong, Liu Yaoning, Jin Yanwen, Li Kaitong, Xiao Yongjiu, Liu Junli, Zhao Huailong, Liu Yue, Li Ping, Song Jibo, Zhang Lu, Gao Yuwei, Kang Sisi, Chen Shoudeng, Ma Qingjun, Bian Xiuwu, Chen Wei, Liu Xuan, Mao Qing, Cao Cheng
Аннотация
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.