Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein.
10.1007/s13238-010-0141-8
- Author:
Junyi JIANG
1
;
Hong TANG
Author Information
1. Key laboratory of Infection and Immunity of Chinese Academy of Sciences, Institute of Biophysics, Beijing 100101, China.
- Publication Type:Journal Article
- MeSH:
Animals;
B-Lymphocytes;
immunology;
metabolism;
Cell Line;
DEAD Box Protein 58;
DEAD-box RNA Helicases;
antagonists & inhibitors;
immunology;
metabolism;
Hep G2 Cells;
Hepatitis B virus;
immunology;
metabolism;
Humans;
I-kappa B Kinase;
antagonists & inhibitors;
immunology;
metabolism;
Immune Evasion;
Immunity, Innate;
Interferon Regulatory Factor-3;
antagonists & inhibitors;
immunology;
metabolism;
Interferon Type I;
antagonists & inhibitors;
immunology;
metabolism;
Mice;
Molecular Targeted Therapy;
Polyubiquitin;
antagonists & inhibitors;
metabolism;
Protein Binding;
immunology;
Sendai virus;
immunology;
metabolism;
Signal Transduction;
immunology;
TNF Receptor-Associated Factor 3;
antagonists & inhibitors;
immunology;
metabolism;
Trans-Activators;
immunology;
metabolism
- From:
Protein & Cell
2010;1(12):1106-1117
- CountryChina
- Language:English
-
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.
