title: Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-beta induction by disrupting the VISA-associated complex.
abstract: 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-kappaB) 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-beta 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.
authors: College of Life Sciences, Modern Virology Center, Wuhan University, Wuhan 430072, China.
authors: Xianmiao
authors: X
authors: Wang
authors: Ying
authors: Y
authors: Li
authors: Aiping
authors: A
authors: Mao
authors: Chao
authors: C
authors: Li
authors: Yongkui
authors: Y
authors: Li
authors: Po
authors: P
authors: Tien
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006515:Hepatitis B virus / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000276:immunology*; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000276:immunology* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016899:Interferon-beta