IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones.-猫眼课题宝

DOI：

10.1016/j.virol.2010.07.041

发表时间：

2010-11

期刊：

Virology

影响因子：

3.7

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

G. Suda;N. Sakamoto;Yasuhiro Itsui;M. Nakagawa;Megumi Tasaka-Fujita;Yusuke Funaoka;Takako Watanabe;S. Nitta;Kei Kiyohashi;Seishin Azuma;S. Kakinuma;K. Tsuchiya;M. Imamura;N. Hiraga;K. Chayama;Mamoru Watanabe

丙型肝炎病毒（HCV）株间干扰素敏感性差异的机制尚未阐明。在这里，我们构建了一个感染性的基因型2b克隆，并使用基因型间同源重组分析了HCV-2b和2a-JFH 1克隆之间干扰素-α敏感性的差异。HCV-2b/JFH 1嵌合病毒能感染Huh7.5.1细胞，对IFN的敏感性明显高于JFH 1。IFN诱导的MxA和25-OAS表达在JFH 1中显著低于2b/JFH 1感染的细胞。在JFH 1感染的细胞中，SOCS 3及其诱导剂IL-6的表达显著高于2b/JFH 1感染的细胞。通过siRNA敲低SOCS 3表达和用抗IL 6抗体预处理来消除JFH 1细胞的IFN抗性。因此，HCV对IFN敏感性的基因型间差异可能与HCV结构蛋白的序列有关，并可通过SOCS 3和IL-6的表达水平来确定。

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.

IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones.

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