Hiraga Nobuhiko, Imamura Michio, Tsuge Masataka, Noguchi Chiemi, Takahashi Shoichi, Iwao Eiji, Fujimoto Yoshifumi, Abe Hiromi, Maekawa Toshiro, Ochi Hidenori, Tateno Chise, Yoshizato Katsutoshi, Sakai Akihito, Sakai Yoshio, Honda Masao, Kaneko Shuichi, Wakita Takaji, Chayama Kazuaki
Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FEBS Lett. 2007 May 15;581(10):1983-7. doi: 10.1016/j.febslet.2007.04.021. Epub 2007 Apr 20.
We developed a reverse genetics system of hepatitis C virus (HCV) genotypes 1a and 2a using infectious clones and human hepatocyte chimeric mice. We inoculated cell culture-produced genotype 2a (JFH-1) HCV intravenously. We also injected genotype 1a CV-H77C clone RNA intrahepatically. Mice inoculated with HCV by both procedures developed measurable and transmissible viremia. Interferon (IFN) alpha treatment resulted in greater reduction of genotype 2a HCV levels than genotype 1a, as seen in clinical practice. Genetically engineered HCV infection system should be useful for analysis of the mechanisms of resistance of HCV to IFN and other drugs.
我们利用感染性克隆和人肝细胞嵌合小鼠开发了丙型肝炎病毒（HCV）1a和2a基因型的反向遗传学系统。我们静脉注射细胞培养产生的2a基因型（JFH-1）HCV。我们还将1a基因型CV-H77C克隆RNA肝内注射。通过这两种方法接种HCV的小鼠均出现了可测量且可传播的病毒血症。正如临床实践中所见，α干扰素治疗导致2a基因型HCV水平的降低幅度大于1a基因型。基因工程HCV感染系统应有助于分析HCV对干扰素和其他药物的耐药机制。
