Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importinα7 is counteracted by TBK1-p62 axis-mediated autophagy  

作　　者：Xuyuan Wang Li Jiang Guangwen Wang Wenjun Shi Yuzhen Hu Bo Wang Xianying Zeng Guobin Tian Guohua Deng Jianzhong Shi Liling Liu Chengjun Li Hualan Chen 

机构地区：[1]College of Veterinary Medicine,Gansu Agricultural University,Lanzhou,730070,China [2]Guangdong Laboratory for Lingnan Modern Agriculture,Guangzhou,510642,China [3]State Key Laboratory of Veterinary Biotechnology,Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Harbin,150069,China

出　　处：《Cellular & Molecular Immunology》2022年第10期1168-1184,共17页中国免疫学杂志（英文版）

基　　金：This investigation was funded by a grant from the Laboratory of Lingnan Modern Agriculture Project(NT2021007 to HC and CL);the National Natural Science Foundation of China(NSFC)(32192453 to CL,32172847 to LJ);the National Key Research and Development Program of China(2021YFD1800203 to HC,2021YFD1800204 to CL);the Natural Science Foundation of Heilongjiang Province(JQ2019C005 to CL);the Central Public-Interest Scientific Institution Basal Research Fund(Y2017JC35 to GT).

摘　　要：As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of IAV.In this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral replication.BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity.Moreover,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import pathway.However,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade BinCARD1.We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic degradation.Overall,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.

关 键 词：Influenza A virus BinCARD1 TRAF3 TBK1 P62 

分 类 号：R511[医药卫生—内科学]