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
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Orthomyxoviridae
/
Receptor Toll-Like 4
/
Gripe Humana
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Corea del Sur