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SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation.
Pan, Pan; Shen, Miaomiao; Yu, Zhenyang; Ge, Weiwei; Chen, Keli; Tian, Mingfu; Xiao, Feng; Wang, Zhenwei; Wang, Jun; Jia, Yaling; Wang, Wenbiao; Wan, Pin; Zhang, Jing; Chen, Weijie; Lei, Zhiwei; Chen, Xin; Luo, Zhen; Zhang, Qiwei; Xu, Meng; Li, Geng; Li, Yongkui; Wu, Jianguo.
  • Pan P; The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Shen M; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Yu Z; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Ge W; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Chen K; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Tian M; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Xiao F; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Wang Z; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Wang J; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Jia Y; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Wang W; The Affiliated ShunDe Hospital of Jinan University, Foshan, China.
  • Wan P; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Zhang J; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Chen W; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Lei Z; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Chen X; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Luo Z; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Zhang Q; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Xu M; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Li G; Foshan Institute of Medical Microbiology, Foshan, China.
  • Li Y; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • Wu J; Foshan Institute of Medical Microbiology, Foshan, China.
Nat Commun ; 12(1): 4664, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338538
ABSTRACT
Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1ß and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Inflammasomes / NLR Family, Pyrin Domain-Containing 3 Protein / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 / Inflammation Type of study: Prognostic study Limits: Animals / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-25015-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Inflammasomes / NLR Family, Pyrin Domain-Containing 3 Protein / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 / Inflammation Type of study: Prognostic study Limits: Animals / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-25015-6