IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones.
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.
Suda
Goki
G
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
Sakamoto
Naoya
N
Itsui
Yasuhiro
Y
Nakagawa
Mina
M
Tasaka-Fujita
Megumi
M
Funaoka
Yusuke
Y
Watanabe
Takako
T
Nitta
Sayuri
S
Kiyohashi
Kei
K
Azuma
Seishin
S
Kakinuma
Sei
S
Tsuchiya
Kiichiro
K
Imamura
Michio
M
Hiraga
Nobuhiko
N
Chayama
Kazuaki
K
Watanabe
Mamoru
M
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
D016898:Interferon-alpha; D015850:Interleukin-6; D012367:RNA, Viral