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

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

  • Signal Transduct Target Ther. 2022 Sep 14;7(1):318. doi: 10.1038/s41392-022-01133-5.
Ting Gao # 1,  Lin Zhu # 1 2,  Hainan Liu # 1,  Xiaopeng Zhang # 1,  Tingting Wang 2,  Yangbo Fu 1,  Hongzhen Li 3,  Qincai Dong 1,  Yong Hu 1,  Zhang Zhang 1,  Jing Jin 2,  Zijing Liu 1,  Weihong Yang 2,  Yaoning Liu 2,  Yanwen Jin 1,  Kaitong Li 3,  Yongjiu Xiao 4,  Junli Liu 1,  Huailong Zhao 1,  Yue Liu 1,  Ping Li 1,  Jibo Song 5,  Lu Zhang 4,  Yuwei Gao 6,  Sisi Kang 7,  Shoudeng Chen 7,  Qingjun Ma 1,  Xiuwu Bian 8,  Wei Chen 1,  Xuan Liu 9,  Qing Mao 10,  Cheng Cao 11
Affiliations

Affiliations

  • 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.
  • 9 Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, 100850, China. [email protected].
  • 10 First Affiliated Hospital, Army Medical University, Chongqing, 400038, China. [email protected].
  • 11 Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, 100850, China. [email protected].
  • # Contributed equally.
PMID: 36100602 DOI: 10.1038/s41392-022-01133-5
Abstract

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.

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