Inhibition of hepatitis C virus infection by interferon-gamma through downregulating claudin-1

• Published in: Journal of interferon & cytokine research Vol. 29; no. 3; pp. 171 - 178
• Main Authors: Wei, Xin, Jia, Zhan-Sheng, Lian, Jian-Qi, Zhang, Ye, Li, Jun, Ma, Li, Ye, Ling, Wang, Jiu-Ping, Pan, Lei, Wang, Ping-Zhong, Bai, Xue-Fan
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.03.2009
• Subjects: Antigens, CD - genetics; Antigens, CD - metabolism; Antiviral Agents - pharmacology; Blotting, Western; Caco-2 Cells; Cell Line, Tumor; Claudin-1; Control; Down-Regulation - drug effects; Fluorescent Antibody Technique; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Health aspects; Hepacivirus - drug effects; Hepacivirus - physiology; Hepatitis C virus; Humans; Interferon gamma; Interferon-gamma - pharmacology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microscopy, Confocal; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Tetraspanin 28; Time Factors; Virus Replication - drug effects
• ISSN: 1079-9907; 1557-7465
• DOI: 10.1089/jir.2008.0040

Hepatitis C virus (HCV) is a serious global health threat and current medical treatment options are limited. Interferon (IFN)-gamma is an important proinflammatory cytokine with antiviral activity. However, the mechanism of IFN-gamma in anti-HCV infection remains unclear. In this study, we investigated the role of IFN-gamma on HCV infection of polarized Caco-2 cells using cell culture-derived HCV (HCVcc). We found that downregulation of claudin-1 (CLDN1) induced by IFN-gamma resulted in disruption of barrier function as demonstrated by measurement of transepithelial electrical resistance and dextran permeability. Further, results from confocal microscopy and Western blot analysis showed that in addition to the reduction of CLDN1 expression, IFN-gamma treatment also led to significant changes in the distribution of CLDN1, CD81, and scavenger receptor class B type I. Moreover, infection assays revealed that IFN-gamma-treated cells showed decreased susceptibility to HCVcc infection. These results suggest a novel mechanism that IFN-gamma may inhibit HCV infection by regulating CLDN1 expression and distribution of HCV receptors.