title: IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones.
abstract: Mechanisms of difference in interferon sensitivity between hepatitis C virus (HCV) strains have yet to be clarified. Here, we constructed an infectious genotype2b clone and analyzed differences in interferon-alpha sensitivity between HCV-2b and 2a-JFH1 clones using intergenotypic homologous recombination. The HCV-2b/JFH1 chimeric virus able to infect Huh7.5.1 cells and was significantly more sensitive to IFN than JFH1. IFN-induced expression of MxA and 25-OAS was significantly lower in JFH1 than in 2b/JFH1-infected cells. In JFH1-infected cells, expression of SOCS3 and its inducer, IL-6, was significantly higher than in 2b/JFH1-infected cells. The IFN-resistance of JFH1 cells was negated by siRNA-knock down of SOCS3 expression and by pretreatment with anti-IL6 antibody. In conclusion, intergenotypic differences of IFN sensitivity of HCV may be attributable to the sequences of HCV structural proteins and can be determined by SOCS3 and IL-6 expression levels.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Goki
authors.initials: G
authors.lastname: Suda
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itsui
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Tasaka-Fujita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Funaoka
authors.forename: Takako
authors.initials: T
authors.lastname: Watanabe
authors.forename: Sayuri
authors.initials: S
authors.lastname: Nitta
authors.forename: Kei
authors.initials: K
authors.lastname: Kiyohashi
authors.forename: Seishin
authors.initials: S
authors.lastname: Azuma
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D002460:Cell Line; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic
chemical_list: D016898:Interferon-alpha; D015850:Interleukin-6; D012367:RNA, Viral