SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation.
Nat Commun
; 12(1): 4664, 2021 08 02.
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Collection:
Bases de données internationales
Base de données:
MEDLINE
Sujet Principal:
Inflammasomes
/
Protéine-3 de la famille des NLR contenant un domaine pyrine
/
Protéines de la nucléocapside des coronavirus
/
SARS-CoV-2
/
COVID-19
/
Inflammation
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
/
Mâle
langue:
Anglais
Revue:
Nat Commun
Thème du journal:
Biologie
/
Science
Année:
2021
Type de document:
Article
Pays d'affiliation:
S41467-021-25015-6
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