Extracellular nucleoprotein exacerbates influenza viruspathogenesis by activating Toll-like receptor 4 and the NLRP3inflammasome  

作　　者：Chang-Ung Kim Yu-Jin Jeong Pureum Lee Moo-Seung Lee Jong-Hwan Park Young-Sang Kim Doo-Jin Kim 

机构地区：[1]Infectious Disease Research Center,Korea Research Institute of Bioscience and Biotechnology(KRIBB),Daejeon,South Korea [2]Department of Biochemistry,Chungnam National University,Daejeon,South Korea [3]Environmental Diseases Research Center,Korea Research Institute of Bioscience and Biotechnology(KRIBB),Daejeon,South Korea [4]University of Science and Technology(UST),Daejeon,South Korea [5]College of Veterinary Medicine,Chonnam National University,Gwangju,South Korea

出　　处：《Cellular & Molecular Immunology》2022年第6期715-725,共11页中国免疫学杂志（英文版）

基　　金：This work was supported by grants from the Bio&Medical Technology Development Program of the National Research Foundation of Korea(NRF)(2018M3A9H4077992);the KRIBB Initiative program(KGM9942112)funded by the Korean government(Ministry of Science&ICT).

摘　　要：Host immune responses, such as those initiated by pattern recognition receptor (PRR) activation, are important for viralclearance and pathogenesis. However, little is known about the interactions of viral proteins with surface PRRs or, moreimportantly, the association of innate immune activation with viral pathogenesis. In this study, we showed that internalinfluenza virus proteins were released from infected cells. Among these proteins, nucleoprotein (NP) played a critical role inviral pathogenesis by stimulating neighboring cells through toll-like receptor (TLR)2, TLR4, and the NLR family pyrin domaincontaining 3 (NLRP3) inflammasome. Through the activation of these PRRs, NP induced the production of interleukin (IL)-1β andIL-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 releasedNP in influenza pathogenesis and highlight the importance of the interactions of internal viral proteins with PRRs in theextracellular compartment during viral pathogenesis.

关 键 词：Influenza virus Viral protein release NUCLEOPROTEIN Toll-like receptor Cyotkine-trypsin cycle 

分 类 号：R392[医药卫生—免疫学]