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(丙型肝炎病毒)表现出严格的范围，只有在人类和实验黑猩猩模型中才能观察到持续感染。在大多数人类和黑猩猩中，感染丙型肝炎病毒会导致持续性和慢性病毒血症，尽管宿主免疫反应正在进行。在人类，重型肝炎、肝硬变、肝细胞癌和死亡是几十年来慢性丙型肝炎相对常见的后果。目前尚不清楚宿主免疫反应在丙型肝炎病毒感染中是否具有保护性，或者实际上宿主反应是导致大多数疾病表现的原因。对人类的初步研究表明，丙型肝炎病毒突变是免疫反应的结果，并导致受感染宿主内形成遗传多样性的病毒群体。这种病毒种群被称为准种，丙型肝炎病毒感染的这种动态特征被认为在很大程度上有助于病毒的持续。该项目是美国国立卫生研究院合作中心建议拨款的一部分，旨在研究与黑猩猩模型中的丙型肝炎病毒清除、丙型肝炎病毒持续存在和肝病活动性相关的病毒和宿主因素。将对16只感染丙型肝炎病毒的动物进行详细的丙型肝炎病毒感染和细胞免疫反应的调查。在其他中心收集的组织将被送往西雅图进行病毒学研究。华盛顿大学病毒性肝炎实验室将在Gretch博士的指导下，使用原位杂交技术对肝脏组织中的丙型肝炎病毒复制动力学进行病毒学分析，以及血液和组织中的丙型肝炎病毒准种进化模式。这项工作将为宿主免疫反应和持续复制的丙型肝炎病毒准种种群之间的动态相互作用提供重要的新信息。