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. 2011 Jan 8;1(12):1106–1117. doi: 10.1007/s13238-010-0141-8

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Junyi Jiang 1,2, Hong Tang 1,✉
PMCID: PMC4875076  PMID: 21213104

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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-010-0141-8 and is accessible for authorized users.

Keywords: hepatitis B virus (HBV), HBV X protein (HBx), deubiquitination, type I interferon

Electronic supplementary material

13238_2010_141_MOESM1_ESM.pdf (413.6KB, pdf)

Supplementary material, approximately 340 KB.

Footnotes

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-010-0141-8 and is accessible for authorized users.

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13238_2010_141_MOESM1_ESM.pdf (413.6KB, pdf)

Supplementary material, approximately 340 KB.

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