HCV REPLICATION AND IMMUNITY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 大约2%的美国人口是慢性感染丙型肝炎病毒（HCV）。 慢性HCV感染导致严重的肝脏疾病，包括肝硬化和肝癌，约20%的感染者。 黑猩猩是HCV感染的唯一动物模型，因此对HCV感染的免疫应答和病毒清除机制的彻底表征对于疫苗开发至关重要。 宿主免疫系统在控制HCV复制中的作用知之甚少。 由表达CD 4或CD 8表面抗原的T细胞介导的细胞免疫应答可能在急性HCV感染的自发消退和正在进行的复制的控制中发挥作用。 相反，T细胞反应差限制但不终止病毒复制，导致慢性感染。 目的是定义急性期病毒复制和免疫应答的动力学，以确定它们之间是否存在时间关系。 此外，将通过给予亚群特异性单克隆抗体在体内耗尽CD 4+和CD 8 + T细胞，以评估其在急性期病毒复制中的作用，并可能作为肝细胞损伤的介质。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 2% of the US population is chronically infected with Hepatitis C virus (HCV). Chronic HCV infections result in significant liver disease including cirrhosis and liver cancer in approximately 20% of infected individuals. The chimpanzee is the only animal model for HCV infection, thus a thorough characterization of the immune response to HCV infections and the mechanism of viral clearance will be critical for vaccine development. The role if host immune system in the control of HCV replication is poorly understood. Cellular immune responses mediated by T cells expressing the CD4 or CD8 surface antigens may play a role in spontaneous resolution of acute HCV infection and in control of ongoing replication. In contrast, a poor T cell response limits but does not terminate virus replication, resulting in chronic infection. The objective is to define the kinetics of acute phase virus replication and immune responses to determine if a temporal relationship exists between them. In addition, CD4+ and CD8+ T cells will be depleted in vivo by administration of subset specific monoclonal antibodies to assess their role in acute phase virus replication and possibly as mediators of hepatocellular injury.