HCV REPLICATION AND IMMUNITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大约2%的美国人口长期感染丙型肝炎病毒。在大约20%的感染者中，慢性丙型肝炎病毒感染会导致严重的肝脏疾病，包括肝硬变和肝癌。黑猩猩是唯一的丙型肝炎病毒感染的动物模型，因此，对丙型肝炎病毒感染的免疫反应和病毒清除机制的彻底表征将对疫苗的开发至关重要。宿主免疫系统在控制丙型肝炎病毒复制中的作用还知之甚少。由表达CD4或CD8表面抗原的T细胞介导的细胞免疫应答可能在自发消退急性丙型肝炎病毒感染和控制正在进行的复制中发挥作用。相比之下，较差的T细胞反应会限制但不会终止病毒复制，从而导致慢性感染。目的是定义急性期病毒复制和免疫反应的动力学，以确定它们之间是否存在时间关系。此外，体内的CD4+和CD8+T细胞将通过注射亚群特异性单抗来耗尽，以评估它们在急性期病毒复制中的作用，并可能作为肝细胞损伤的媒介。

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.