MODEL SYSTEMS FOR IN VITRO REPLICATION OF HEPATITIS C VIRUS

丙型肝炎病毒体外复制模型系统

• 批准号: 5206025
• 负责人: ROBERT E LANFORD
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5206025
• 关键词: Pan; antibody formation; antiviral antibody; bioengineering /biomedical engineering; biotechnology; cooperative study; hepatitis C; molecular cloning; nucleic acid sequence; polymerase chain reaction; tissue /cell culture; virus RNA; virus replication

Hepatitis C virus (HCV) infections represent a major worldwide health problem with an estimated 0.5-1.5% of the population infected. Approximately 70% of infected individuals develop chronic infections that may lead to cirrhosis and hepatocellular carcinoma. The introduction of diagnostic assays for antibodies to HCV has reduced the risk of transfusion associated HCV, but will have little impact on the spread of the disease by other routes. The development of efficacious antiviral treatments for this agent are essential to control the spread of the disease. A greater understanding of the replicative mechanisms of the virus will be essential in the development of antiviral therapies. A critical need exists for model systems to study replicative functions of the virus as well as tissue culture systems permissive for HCV replication. This proposal directly addresses these needs. The specific aims are 1) to construct full length clones of HCV and evaluate the clones for infectivity in a variety of cell culture systems; 2) to adapt HCV for replication in continuous cell lines by co- cultivation of cell lines with HCV-infected primary hepatocytes; and 3) to define the 3' HCV sequences required in cis for negative strand RNA replication. An additional aim is 4) to evaluate HCV-infected chimpanzees for the presence of antibody negative viral carriers and for the antibody response to native envelope proteins. The long term goals are to develop a better understanding at a molecular level of HCV replication. The model systems developed for these studies will be of great value in the evaluation of antiviral agents and will provide new targets for the development of antivirals. Accomplishments of the goals of this proposal will significantly impact the likelihood of developing efficacious treatments for this disease.

丙型肝炎病毒（HCV）感染代表了全球主要健康 估计有0.5-1.5％的人口感染的问题。 大约70％的感染者发展出慢性感染 这可能导致肝硬化和肝细胞癌。 这 引入HCV抗体的诊断测定已减少 与HCV相关的输血风险，但对 通过其他路线传播疾病。 有效的发展 该药物的抗病毒治疗对于控制扩散至关重要 疾病。 对复制机制有更深入的了解 该病毒的发展对于抗病毒的发展至关重要 疗法。 对于模型系统而存在的关键需求 病毒和组织培养系统的复制功能 HCV复制的允许性。 该建议直接解决了这些问题 需要。 具体目的是1）构建HCV的全长克隆 并评估克隆在多种细胞培养中的感染性 系统； 2）适应HCV以在连续细胞系中复制 用HCV感染的原发性肝细胞培养细胞系； 3） 定义CIS中所需的3'HCV序列的负链RNA 复制。 另一个目标是4）评估HCV感染的 黑猩猩的存在，用于存在抗体阴性病毒载体和 对天然包膜蛋白的抗体反应。长期目标 是在HCV的分子水平上建立更好的理解 复制。 这些研究开发的模型系统将是 在评估抗病毒剂的巨大价值，并将提供新的 开发抗病毒药的目标。 目标的成就 该提议将极大地影响发展的可能性 对这种疾病的有效治疗方法。