title: Specific inhibition of hepatitis C virus replication by cyclosporin A.
abstract: The difficulty in eradicating hepatitis C virus (HCV) infection is attributable to the limited treatment options against the virus. Recently, cyclosporin A (CsA), a widely used immunosuppressive drug, has been reported to be effective against HCV infection [J. Gastroenterol. 38 (2003) 567], although little is understood about the mechanism of its action against HCV. In this study, we investigated the anti-viral effects of CsA using an HCV replicon system. Human hepatoma Huh7 cells were transfected with an HCV replicon expressing a chimeric gene encoding a luciferase reporter and neomycin phosphotransferase (Huh7/Rep-Feo). Treatment of the Huh7/Rep-Feo cells with CsA resulted in suppression of the replication of the HCV replicon in a dose-dependent manner, with an IC50 of approximately 0.5 microg/ml. There were no changes in the rate of cell growth or viability, suggesting that the effect of CsA against HCV is specific and not due to cytotoxicity. In contrast, FK506, another immunosuppressive drug, did not suppress HCV replication. CsA did not activate interferon-stimulated gene responses, suggesting that its action is independent of that of interferon. In conclusion, CsA inhibits HCV replication in vitro specifically at clinical concentrations. Further defining its mode of action against HCV replication potentially may be important for identifying novel molecular targets to treat HCV infection.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kanazawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Maekawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamashiro
authors.forename: Cheng Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itsui
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology*; D016679:Genome, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D019868:Kanamycin Kinase / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012093:Replicon / Q000187:drug effects / Q000235:genetics; D016559:Tacrolimus / Q000494:pharmacology; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; D012313:RNA; D016572:Cyclosporine; D008156:Luciferases; D019868:Kanamycin Kinase; D016559:Tacrolimus