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Cited by 501

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation

Open access
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·2021·Nature Communications

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-1β 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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Crossref · 10.1038/s41467-021-25015-6

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Metadata

Authors
Pan, P., Shen, M., Yu, Z., Ge, W., Chen, K., Tian, M., Xiao, F., Wang, Z., Wang, J., Jia, Y., Wang, W., Wan, P., Zhang, J., Chen, W., Lei, Z., Chen, X., Luo, Z., Zhang, Q., Xu, M., Li, G., Li, Y., & Wu, J.
Venue
Nature Communications
Published
2021-08-02
Volume
12
Issue
1
Pages
4664-4664
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3191928958
Cited by
501
References
11
FWCI
25.69
Type
journal article
Language
en
Open access
gold

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