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

描述（由申请人提供）： PI：Hugo R.罗森，医学博士/丹佛弗吉尼亚州优秀评审奖：CD 8 + T细胞在丙型肝炎病毒感染恢复中的功能属性全世界约有2亿人患有慢性HCV感染。HCV在高达80%的感染者中持续存在。仅在美国，未来10- 20年的直接医疗成本负担预计将超过100亿美元，而社会总成本将翻一番。HCV是肝癌和肝移植的主要病因。尽管新疗法提高了持续应答率，但很大一部分患者（约50%）对抗病毒治疗无效或出现显著的药物毒性，因此仍有疾病进展的风险。了解HCV-宿主相互作用是对抗这种病毒和开发改进的疗法所必需的。虽然来自感染早期阶段的数据提供了最大的机制见解，但急性HCV通常无法识别，因为症状通常较轻或不存在。详细的前瞻性研究急性和发展中的HCV感染，需要划定逃逸突变在HCV持久性的作用，以及定义的免疫学和病毒学因素控制病毒的演变。特别是，仔细剖析这些因素将是至关重要的设计任何有效的T细胞为基础的治疗。

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.