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Protein & Cell ; (12): 1106-1117, 2010.
Artículo en Inglés | WPRIM | ID: wpr-757676

RESUMEN

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.


Asunto(s)
Animales , Humanos , Ratones , Linfocitos B , Alergia e Inmunología , Metabolismo , Línea Celular , Proteína 58 DEAD Box , ARN Helicasas DEAD-box , Alergia e Inmunología , Metabolismo , Células Hep G2 , Virus de la Hepatitis B , Alergia e Inmunología , Metabolismo , Quinasa I-kappa B , Alergia e Inmunología , Metabolismo , Evasión Inmune , Inmunidad Innata , Factor 3 Regulador del Interferón , Alergia e Inmunología , Metabolismo , Interferón Tipo I , Alergia e Inmunología , Metabolismo , Terapia Molecular Dirigida , Poliubiquitina , Metabolismo , Unión Proteica , Alergia e Inmunología , Virus Sendai , Alergia e Inmunología , Metabolismo , Transducción de Señal , Alergia e Inmunología , Factor 3 Asociado a Receptor de TNF , Alergia e Inmunología , Metabolismo , Transactivadores , Alergia e Inmunología , Metabolismo
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