Extracellular nucleoprotein exacerbates influenza virus pathogenesis by activating Toll-like receptor 4 and the NLRP3 inflammasome.
Cell Mol Immunol
; 19(6): 715-725, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35459853
ABSTRACT
Host immune responses, such as those initiated by pattern recognition receptor (PRR) activation, are important for viral clearance and pathogenesis. However, little is known about the interactions of viral proteins with surface PRRs or, more importantly, the association of innate immune activation with viral pathogenesis. In this study, we showed that internal influenza virus proteins were released from infected cells. Among these proteins, nucleoprotein (NP) played a critical role in viral pathogenesis by stimulating neighboring cells through toll-like receptor (TLR)2, TLR4, and the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Through the activation of these PRRs, NP induced the production of interleukin (IL)-1ß and IL-6, which subsequently led to the induction of trypsin. Trypsin induced by NP increased the infectivity of influenza virus, leading to increases in viral replication and pathology upon subsequent viral infection. These results reveal the role of released NP in influenza pathogenesis and highlight the importance of the interactions of internal viral proteins with PRRs in the extracellular compartment during viral pathogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Orthomyxoviridae
/
Receptor 4 Toll-Like
/
Influenza Humana
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Mol Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Coréia do Sul