Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-β induction by disrupting the VISA-associated complex  

作　　者：Xianmiao Wang Ying Li Aiping Mao Chao Li Yongkui Li Po Tien 

机构地区：[1]College of Life Sciences,Modern Virology Center,Wuhan University,Wuhan 430072,China

出　　处：《Cellular & Molecular Immunology》2010年第5期341-348,共8页中国免疫学杂志（英文版）

基　　金：supported by grants from the 973 Program of China(No.2006CB504301).

摘　　要：Viral RNAs produced during viral infection are recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene-I(RIG-I)and melanoma differentiation-associated gene 5(MDA5).A central adapter protein downstream of RIG-I and MDA5 is the mitochondrial membrane protein virus-induced signaling adaptor(VISA),which mediates the induction of type I interferons(IFNs)through the activation of transcription factors such as nuclear factor-kappaB(NF-kB)and IFN-regulatory factor-3(IRF3).Here we found that hepatitis B virus(HBV)-encoded X protein(HBx)acts as an inhibitor of virus-triggered IRF3 activation and IFN-b induction.Reporter and plaque assays indicate that HBx inhibits signaling by components upstream but not downstream of VISA.Immunoprecipitation experiments indicate that HBx interacts with VISA and disrupts the association of VISA with its upstream and downstream components.These findings suggest that HBx acts as a suppressor of virus-triggered induction of type I IFNs,which explains the observation that HBV causes transient and chronic infection in hepatocytes but fails to activate the pattern recognition receptor-mediated IFN induction pathways.

关 键 词：HBX innate immunity signal transduction type I interferons VISA 

分 类 号：R73[医药卫生—肿瘤]