Modeling GBV-B Replication in Immortalized Cell Lines

永生化细胞系中 GBV-B 复制的建模

• 批准号: 6560511
• 负责人: VICTOR E. BUCKWOLD
• 金额: $ 11.49万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-19 至 2004-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6560511
• 关键词: Callithricidae; Flaviviridae; antiviral agents; cell line; cell transformation; drug screening /evaluation; high throughput technology; liver cells; technology /technique development; tissue /cell culture; virus replication

DESCRIPTION (provided by applicant): There is no robust cell culture system in which the hepatitis C virus (HCV) can replicate. As such, surrogate models of HCV replication are frequently used for the evaluation of antiviral compounds. The GB virus B (GBV-B) is the closest related virus phylogenetically with HCV and is an attractive surrogate model for HCV drug development efforts. Unfortunately, GBV-B can so far only be grown in primary hepatocytes taken from small non-human primates. This makes the current GBV-B antiviral assay difficult to perform, expensive, and not amenable to high-throughput (HTP) screening. This application aims to develop a robust cell culture model of GBV-B replication utilizing immortalized cell lines. The specific aims of this project are to immortalize the primary hepatocytes of GBV-B-susceptible animals, identify if these and other established cell lines can support GBV-B replication in vitro, and to standardize and validate the model system produced for use in the evaluation of antiviral agents. This project will make the GBV-B antiviral assay widely available, affordable, and appropriate for HTP applications. This will facilitate the discovery and development of new anti-HCV drugs that may improve the quality of life for HCV-infected patients.

描述（由申请人提供）：没有健壮的细胞培养系统可供丙型肝炎病毒（HCV）复制。因此，HCV 复制的替代模型经常用于评估抗病毒化合物。 GB 病毒 B (GBV-B) 是在系统发育上与 HCV 最相关的病毒，并且是 HCV 药物开发工作的一个有吸引力的替代模型。不幸的是，GBV-B 迄今为止只能在取自小型非人类灵长类动物的原代肝细胞中生长。这使得当前的 GBV-B 抗病毒检测难以进行、昂贵且不适合高通量 (HTP) 筛选。该应用旨在利用永生化细胞系开发 GBV-B 复制的稳健细胞培养模型。该项目的具体目标是永生化 GBV-B 易感动物的原代肝细胞，确定这些细胞系和其他已建立的细胞系是否可以支持 GBV-B 体外复制，并对用于评估抗病毒药物的模型系统进行标准化和验证。该项目将使 GBV-B 抗病毒检测广泛可用、价格实惠且适合 HTP 应用。这将有助于发现和开发新的抗丙肝病毒药物，从而改善丙肝病毒感染患者的生活质量。