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- Title
Hepatitis C virus impairs TLR3 signaling and inhibits IFN-λ 1 expression in human hepatoma cell line.
- Authors
Wang, Yizhong; Li, Jieliang; Wang, Xu; Ye, Li; Zhou, Yu; Thomas, Rebecca M; Ho, Wenzhe
- Abstract
Toll-like receptor 3 (TLR3) activation plays an important role in the innate immune responses to viral infections. We show here that the activation of TLR3 signaling pathway by poly I:C, a synthetic mimic of dsRNA, could induce high-level expression of interferon (IFN)-λ1 in a hepatoma cell line. The induced IFN-λ1 contributed to poly I:C-mediated inhibition of hepatitis C virus (HCV) Japanese fulminant hepatitis-1 (JFH-1) replication in Huh7 cells. This inhibitory effect of poly I:C on HCV replication, however, was compromised by HCV infection of Huh7 cells. Investigation of the mechanisms showed that HCV infection suppressed the expression of poly I:C-induced IFN-λ1 and IFN-stimulated genes [IFN-stimulated gene 56 (ISG-56), myxovirus resistance A (MxA) and 2′-5′-oligoadenylate synthetase1 (OAS-1))], the key antiviral elements in IFN signaling pathway. Among the HCV nonstructural (NS) proteins tested, NS3/4A, NS5A and NS5B had the ability to inhibit poly I:C-induced IFN-λ1 expression in Huh7 cells. These observations provide the experimental evidence that HCV and its proteins impair TLR3 signaling and inhibit intracellular IFN-λ1/ISG expression in a hepatoma cell line, which may account for HCV persistence in the liver.
- Subjects
HEPATITIS C; TOLL-like receptors; NATURAL immunity; INTERFERONS; GENE expression; HEPATOCELLULAR carcinoma; CANCER cells; CELLULAR signal transduction
- Publication
Innate Immunity, 2014, Vol 20, Issue 1, p3
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425913478991