Extracellular Nucleoprotein Exacerbates Influenza Virus Pathogenesis by Activating Toll-like Receptor 4 and the NLRP3 Inflammasome

Overview

Journal Cell Mol Immunol

Date 2022 Apr 23

PMID 35459853

Authors

Chang-Ung Kim

Yu-Jin Jeong

Pureum Lee

Moo-Seung Lee

Jong-Hwan Park

Young-Sang Kim

Doo-Jin Kim

Affiliations

Soon will be listed here.

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)-1β 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.

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