Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein
Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein
Junyi Jiang1,2, Hong Tang1()
1. Key laboratory of Infection and Immunity of Chinese Academy of Sciences, Institute of Biophysics, Beijing 100101, China; 2. Graduate School of Chinese Academy of Sciences, Beijing 100049, China
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.
. Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein[J]. Protein & Cell, 2010, 1(12): 1106-1117.
Junyi Jiang, Hong Tang. Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein. Prot Cell, 2010, 1(12): 1106-1117.
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