Affiliation:
1. The Center for Animal Experiment/ABSL-3 Laboratory, Wuhan University, Hubei, People's Republic of China
2. Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA
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 synthetase 1 (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.
Subject
Infectious Diseases,Cell Biology,Molecular Biology,Immunology,Microbiology
Cited by
20 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献