On the development of the system to screen new anti-HCV drugs

丙型肝炎病毒是慢性肝炎发展的病原体。由于慢性肝炎患者发生肝细胞癌的发生率高于未感染者，HCV感染在该病的发展中起着重要作用。预防丙型肝炎病毒感染以及从丙型肝炎病毒携带者中根除丙型肝炎病毒是预防该病发病的主要途径。然而，缺乏在适当细胞系中培养HCV的系统阻碍了HCV疫苗和抗HCV药物的开发。我们从丙型肝炎病毒增殖不良的细胞中分离出丙型肝炎病毒基因组，并用它建立了一种丙型肝炎病毒基因组有效自我复制的细胞系。利用这些细胞，我们分析了干扰素对HCV基因组增殖的影响。我们获得了具有干扰素抗HCV增殖特性的细胞系。由于干扰素对HCV增殖作用的分子机制尚不清楚，该系统可能有助于阐明干扰素对HCV增殖作用的确切机制。此外，我们还发现HCV复制复合体可能位于内质网膜上，并受到脂质结构的保护。这一信息也可用于开发具有抗hcv功能的新药物。

Hepatitis C virus is a causative agent for the development of chronic hepatitis. Since the incidence of the development of hepatocellular carcinoma among the patients with chronic hepatitis is higher than those with uninfected individuals, HCV infection plays important roles on the development of the disease. Prevention of HCV infection as well as eradication of HCV from HCV carriers is the prominent ways to prevent the onset of the disease. However the lack of the system to culture HCV in an appropriate cell lines hampers the development of HCV vaccine and anti-HCV agents. We isolated the HCV genome from cells in which HCV proliferates poorly and used it to establish a cell line in which HCV genome self-replicates efficiently. Using these cells, we have analyzed the effect of interferon on HCV genome proliferation. We obtained the cell lines that acquired the character to show the resistance to interferon for HCV proliferation. Because that the molecular mechanisms of the interferon action to HCV proliferation is not demonstrated clearly yet, this system may help to clarify the precise mechanism of interferon for HCV proliferation. Moreover, we found that HCV replicating complex is localized on possibly membrane of endoplasmic reticulum and is protected by lipid structure. This information may also be applied to develop a new agent with anti-HCV function.