Interaction between the HCVNS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses

被引：100

作者：

Otsuka, M ^{[1
]}

Kato, N ^{[1
]}

Moriyama, M ^{[1
]}

Taniguchi, H ^{[1
]}

Wang, Y ^{[1
]}

Dharel, N ^{[1
]}

Kawabe, T ^{[1
]}

Omata, M ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, Tokyo 1138655, Japan

来源：

HEPATOLOGY | 2005年 / 41卷 / 05期

关键词：

D O I：

10.1002/hep.20666

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

The persistent nature of hepatitis C virus (HCV) infection suggests that HCV encodes proteins that enable it to overcome host antiviral responses. Toll-like receptor 3 (TLR3)-mediated signaling, which recognizes the double-stranded RNA that is produced during viral replication and induces type I interferons, including interferon beta (IFN-beta), is crucial to the host defense against viruses. Recent studies suggest that a TIR domain-containing adaptor protein, TRIF, and two protein kinases, TANK-binding kinase-1 (TBK1) and I kappa B kinase-epsilon (IKK epsilon), play essential roles in TLR3-mediated IFN-beta production through the activation of the transcriptional factor interferon regulatory factor 3 (IRF-3). We report that the HCV NS3 protein interacts directly with TBK1, and that this binding results in the inhibition of the association between TBK1 and IRF-3, which leads to the inhibition of IRF-3 activation. In conclusion, these results suggest the mechanisms of the inhibition of the innate immune responses of HCV infection by NS3 protein.

引用

页码：1004 / 1012

页数：9

共 37 条

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