HCV REPLICATION AND IMMUNITY

点击翻译按钮获取中文摘要

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.