Functional attributes of CD8+ T cells in recovery of hepatitis C virus infection

描述(由申请人提供)： PI：雨果·R·罗森，医学博士/丹佛，弗吉尼亚州，荣誉审查补助金：CD8+T细胞在丙型肝炎病毒感染恢复中的功能属性全世界大约有2亿人患有慢性丙型肝炎病毒感染。高达80%的感染者感染了丙型肝炎病毒。仅在美国，未来10-20年的直接医疗成本预计将超过100亿美元，社会总成本将翻一番。丙型肝炎病毒是导致肝癌和肝移植的主要病因。尽管新的治疗方法提高了持续应答率，但很大比例(~50%)的患者对抗病毒治疗无效或出现显著的药物毒性，因此仍面临疾病进展的风险。需要了解丙型肝炎病毒与宿主之间的相互作用，以对抗这种病毒并开发改进的治疗方法。虽然从感染的早期阶段获得的数据提供了最大的机械性见解，但急性丙型肝炎往往没有被识别出来，因为症状通常很轻微或没有。需要对急性和演变中的丙型肝炎病毒感染进行详细的前瞻性研究，以阐明逃逸突变在丙型肝炎病毒持续存在中的作用，以及确定控制病毒进化的免疫学和病毒学因素。特别是，仔细分析这些因素对于设计任何有效的基于T细胞的治疗将是至关重要的。

DESCRIPTION (provided by applicant): PI: Hugo R. Rosen, MD/ Denver VA Title of Merit Review Grant: Functional attributes of CD8+ T cells in recovery of hepatitis C virus infection Approximately 200 million throughout the world have chronic HCV infection. HCV persists in up to 80% of people infected. In the US alone, the burden over the next 10- 20 years is expected to reach over $10 billion in direct medical costs and double this in overall societal costs. HCV is a leading etiology of liver cancer and cause for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (~50%) fail to respond to antiviral treatment or develop significant drug toxicity, thus remaining at risk for disease progression. An understanding of HCV-host interactions is required to combat this virus and to develop improved therapies. Although data derived from the earliest stages of infection provide the greatest mechanistic insights, acute HCV is often unrecognized because symptoms are usually mild or absent. Detailed prospective studies of acute and evolving HCV infection are required to delineate the role of escape mutations in HCV persistence, as well as to define the immunological and virological factors governing viral evolution. In particular, careful dissection of these factors will be critical to the design of any effective T-cell based therapy.