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.
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DOI：
10.1007/s13238-010-0141-8
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发表时间：
2010-12
期刊：
影响因子：
21.1
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Jiang J;Tang H
B型肝炎病毒（Hepatitis B virus，HBV）被认为是一种隐形病毒，能在人体肝脏内高效入侵和复制，而宿主的先天性抗病毒免疫却无法发现。在这里，我们表明，I型干扰素（IFN）的诱导，但不是它的下游信号被阻断HBV复制HepG2.2.15细胞。这种效应可能部分归因于HBV X蛋白（HBx），其损害仙台病毒（SeV）和病毒传感器信号传导中涉及的组分对IFNβ启动子的激活。作为去泛素化酶（DUB），HBx从除TANK结合激酶1（TBK 1）之外的许多蛋白质切割Lys 63连接的多聚泛素链。它结合并解偶联视黄酸诱导基因I（RIG I）和TNF受体相关因子3（TRAF 3），导致它们与下游衔接子CARDIF或TBK 1激酶解离。除了RIG I和TRAF 3，HBx还与CARDIF、TRIF、NEMO、TBK 1、B细胞中κ轻链多肽基因增强子的抑制剂、激酶IKKi（IKKi）和干扰素调节因子3（IRF 3）相互作用。我们的数据表明，HBx可以靶向多个信号通路点，以负调节I型IFN的产生。可通过10.1007/s13238-010-0141-8获取本文的补充材料，授权用户可访问。
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. Supplementary material is available for this article at 10.1007/s13238-010-0141-8 and is accessible for authorized users.