Virus specific T cells in replication/evolution of HCV

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，仅在人类和实验黑猩猩模型中观察到持续感染。在大多数人类和黑猩猩中，尽管宿主免疫应答持续，但HCV感染导致持续和慢性病毒血症。在人类中，重度肝炎、肝硬化、肝细胞癌和死亡是慢性丙型肝炎几十年来相对常见的后果。目前尚不清楚宿主免疫应答在HCV感染中是否具有保护性。或者事实上，宿主反应是大多数疾病表现的原因。对人类的初步研究表明，HCV突变是由免疫反应引起的，并导致感染宿主内形成遗传多样性的病毒群体。这样的病毒群体被称为准种，HCV感染的这种动态特征被认为是病毒持续存在的主要原因。该项目是美国国立卫生研究院合作中心资助的一部分，旨在研究与黑猩猩模型中HCV清除、HCV持续性和肝病活动相关的病毒和宿主因素。将对16只HCV感染动物进行HCV感染和细胞免疫应答的详细研究。在其他中心采集的组织将转送至西雅图进行病毒学研究。将在Dr. Gretch的指导下，在华盛顿大学病毒性肝炎实验室使用原位杂交技术对肝组织中HCV复制动力学进行病毒学分析，并对血液和组织中HCV准种演变模式进行分析。这项工作将提供重要的新信息之间的动态相互作用的主机免疫反应和持续复制的HCV准种群体。

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.