BEND6 promotes RNA viruses'replication by inhibiting innate immune responses  

作　　者：Tong Chen Ling Ding Shaoyu Tu Huimin Sun Jiahui Zou Aotian Ouyang Meijun Jiang Yi Feng Meilin Jin Huanchun Chen Hongbo Zhou 

机构地区：[1]National Key Laboratory of Agricultural Microbiology,College of Veterinary Medicine,Huazhong Agricultural University,Wuhan,430070,China [2]Frontiers Science Center for Animal Breeding and Sustainable Production,Wuhan,430070,China [3]Hubei Hongshan Laboratory,Wuhan,430070,China [4]Key Laboratory of Preventive Veterinary Medicine in Hubei Province,The Cooperative Innovation Center for Sustainable Pig Production,Wuhan,430070,China

出　　处：《Science China(Life Sciences)》2025年第4期1073-1083,共11页中国科学(生命科学英文版)

基　　金：supported by the National Key Research and Development Program of China(2021YFD1800204);the National Natural Science Foundation of China(32025036);the Fundamental Research Funds for the Central Universities(2662023PY005);Hubei Hongshan Laboratory(2022hszd005);the earmarked fund for CARS-41;the Natural Science Foundation of Hubei Province(2021CFA016)。

摘　　要：Innate immunity serves as a crucial defense mechanism against invading pathogens,yet its negative regulatory network remains under explored.In this study,we identify BEN domain-containing protein 6(BEND6)as a novel negative regulator of innate immunity through a genome-scale CRISPR knockout screen for host factors essential for viral replication.We show that BEND6 exhibits characteristics of an interferon-stimulated gene(ISG),with its mRNA and protein levels upregulated by RNA virus-induced IFN-β.BEND6 targets IRF3 and inhibits its recruitment by TBK1,thus preventing IRF3 phosphorylation and dimerization.Additionally,BEND6 directly binds to ISRE,thereby hindering the DNA binding activity of IRF3 and blocking the subsequent activation of IFN-βtranscription.Taken together,our study reveals the mechanism of BEND6 in promoting the replication of various RNA viruses and provides a potential therapeutic target for RNA virus infection.

关 键 词：innate immunity BEND6 RNAvirus IRF3 IFN-Β 

分 类 号：R392[医药卫生—免疫学]