期刊
INNATE IMMUNITY
卷 20, 期 1, 页码 3-11出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425913478991
关键词
Hepatitis C virus; interferon-lambda; IFN-stimulated genes; poly I:C; Toll-like receptor 3
资金
- National Institutes of Health [DA12815, DA22177, DA27550]
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)-1 in a hepatoma cell line. The induced IFN-1 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-1 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-1 expression in Huh7 cells. These observations provide the experimental evidence that HCV and its proteins impair TLR3 signaling and inhibit intracellular IFN-1/ISG expression in a hepatoma cell line, which may account for HCV persistence in the liver.
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