Therapetic strategy for chronic hepatitis C by inducing apoptosis of hepatocyte infected with hepatitis C virus

为研究丙型肝炎病毒（HCV）感染对肝细胞的影响，我们建立了几个表达HCV核心基因的永久性肝细胞克隆。这些克隆的微阵列分析揭示了一对夫妇的基因表达的HCV核心表达克隆调制。我们应用Nothing印迹分析来确认在HCV核心表达克隆中表达下调的2个基因以及表达上调的3个基因。我们目前正在分析这些基因在肝细胞中的作用。我们还研究了HCV核心表达对细胞凋亡和细胞增殖的影响。HCV核心基因的表达不影响细胞凋亡，但通过抑制G1/S转换而显著抑制肝细胞增殖。这些结果表明，HCV感染抑制肝细胞增殖，但不影响肝细胞凋亡，提高了HCV感染的肝细胞可以通过凋亡刺激根除的可能性。

To investigate influence of hepatitis C virus (HCV) infection on hepatocyte, we established several permanent hepatocyte clones that express HCV core gene. Microarray analysis of these clones revealed a couple of gene of which expression was modulated in HCV core-expressing clones. We applied Nothern blot analysis to confirm 2 genes of which expression was downrgulated as well as 3 genes of which expression was upregulated in HCV core-expressing clones. We are currently analyzing the role of these genes in hepatocytes. We also investigated the effect of HCV core expression on apoptosis as well as cell proliferation. Expression of HCV core gene did not affect apoptosis, but significantly retarded proliferation of hepatocyte by inhibiting G1/S transition. These results suggest that infection of HCV inhibits hepatocyte proliferation but does not affect apoptosis of hepatocytes, raising the possibility that HCV-infected hepatocytes can be eradicated by apoptotic stimuli.