title: Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein.
abstract: Hepatitis B virus (HBV) is regarded as a stealth virus, invading and replicating efficiently in human liver undetected by host innate antiviral immunity. Here, we show that type I interferon (IFN) induction but not its downstream signaling is blocked by HBV replication in HepG2.2.15 cells. This effect may be partially due to HBV X protein (HBx), which impairs IFNβ promoter activation by both Sendai virus (SeV) and components implicated in signaling by viral sensors. As a deubiquitinating enzyme (DUB), HBx cleaves Lys63-linked polyubiquitin chains from many proteins except TANK-binding kinase 1 (TBK1). It binds and deconjugates retinoic acid-inducible gene I (RIG I) and TNF receptor-associated factor 3 (TRAF3), causing their dissociation from the downstream adaptor CARDIF or TBK1 kinase. In addition to RIG I and TRAF3, HBx also interacts with CARDIF, TRIF, NEMO, TBK1, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon (IKKi) and interferon regulatory factor 3 (IRF3). Our data indicate that multiple points of signaling pathways can be targeted by HBx to negatively regulate production of type I IFN.
authors.affiliation: Key laboratory of Infection and Immunity of Chinese Academy of Sciences, Institute of Biophysics, Beijing 100101, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D057131:Immune Evasion; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D058990:Molecular Targeted Therapy; D025821:Polyubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D048008:TNF Receptor-Associated Factor 3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology* / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D011971:Receptors, Immunologic; D048008:TNF Receptor-Associated Factor 3; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D025821:Polyubiquitin; D051550:I-kappa B Kinase; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases