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

抗HCV新药筛选系统的研制

基本信息

批准号：
13557024
负责人：
SHIMOTOHNO Kunitada
金额：
$ 8.9万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557024/
关键词：
hepatitis C virus chronic hepatitis HCV genome replication replicon ゲノム RT-PCR リバビリン複製複合体

项目摘要

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.

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，因此丙型肝炎病毒感染在疾病的发展中起着重要作用。预防HCV感染以及从HCV携带者中根除HCV是预防疾病发生的主要途径。然而，缺乏在合适的细胞系中培养HCV的系统阻碍了HCV疫苗和抗HCV药物的开发。我们从HCV增殖不良的细胞中分离出HCV基因组，并将其用于建立HCV基因组有效自我复制的细胞系。使用这些细胞，我们分析了干扰素对HCV基因组增殖的影响。我们获得的细胞系获得的特性，显示干扰素的HCV增殖的抗性。由于干扰素对HCV增殖作用的分子机制尚不清楚，本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，我们发现HCV复制复合物可能位于内质网膜上，并受到脂质结构的保护。这些信息也可用于开发具有抗HCV功能的新药物。