Virus specific T cells in replication/evolution of HCV

HCV 复制/进化中的病毒特异性 T 细胞

• 批准号: 6652718
• 负责人: David Richard Gretch
• 金额: $ 43.42万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652718
• 关键词: Pan; T lymphocyte; biochemical evolution; cellular immunity; cooperative study; disease /disorder model; genetic strain; hematopoietic tissue; hepatitis C; hepatitis C virus; liver; virus genetics; virus replication

Chronic hepatitis C is an important cause of severe liver disease in the United States and throughout the world. Hepatitis C virus (HCV) shows a strict range, with persistent infection observed only in humans and the experimental chimpanzee model. In the majority of humans and chimpanzees, infection with HCV results in persistent and chronic viremia despite an ongoing host immune response. In humans, severe hepatitis, liver cirrhosis, hepatocellular carcinoma and death are relatively common consequences of chronic hepatitis C over several decades. It is presently unknown whether the host immune response is protective in HCV infection., or in fact the host response is responsible for most of the disease manifestations. Preliminary studies in humans suggest the HCV mutations result from immune responses and lead to the formation of genetically diverse viral populations within the infected host. Such viral populations are termed quasispecies, and this dynamic feature of HCV infection is thought to contribute in a major way to viral persistence. This project is part of a proposed NIH Cooperative Center grant aimed at studying viral and host factors related to HCV clearance, HCV persistence, and activity of liver disease in the chimpanzee model. Detailed investigation of HCV infection and cellular immune responses will be conducted on 16 animals with HCV infection. Tissue collected at other centers will be forwarded to Seattle for virology studies. Virological analyses of HCV replication kinetics in liver tissue using in situ hybridization techniques, and HCV quasispecies evolution patterns in blood and tissue will be conducted at the University of Washington Viral Hepatitis Laboratory under the direction of Dr. Gretch. The work will provide important new information on the dynamic interactions between the host immune response and the persistently replicating HCV quasispecies populations.

慢性丙型肝炎是美国和全世界严重肝病的重要原因。丙型肝炎病毒（HCV）显示出严格的范围，仅在人类和实验性黑猩猩模型中观察到持续的感染。在大多数人和黑猩猩中，尽管持续的宿主免疫反应持续，但HCV感染带来了持续性和慢性病毒性。在人类中，严重的肝炎，肝硬化，肝细胞癌和死亡是慢性乙型肝炎的几十年来相对常见的后果。目前尚不清楚宿主免疫反应在HCV感染中是否具有保护作用。人类的初步研究表明，HCV突变是由免疫反应引起的，并导致受感染宿主中遗传多样的病毒群体形成。这种病毒种群被称为准特性，而HCV感染的这种动态特征被认为以主要方式导致病毒持久性。该项目是拟议的NIH合作中心赠款的一部分，该基金旨在研究与黑猩猩模型中有关HCV清除，HCV持久性和肝脏疾病活动有关的宿主因素。 HCV感染和细胞免疫反应的详细研究将对16只具有HCV感染的动物进行。在其他中心收集的组织将被转发给西雅图进行病毒学研究。使用原位杂交技术对肝组织中HCV复制动力学的病毒学分析以及血液和组织中的HCV准化学演化模式将在华盛顿大学病毒肝炎实验室在Gretch博士的方向下进行。这项工作将提供有关宿主免疫反应与持续复制HCV准人群之间动态相互作用的重要新信息。