Functional Activities of HCV Core Protein

描述(申请人提供)：丙型肝炎病毒(丙型肝炎病毒)通常会引起 长期和持续性感染与肝细胞癌 癌症(肝癌)和丙型肝炎病毒感染已经被注意到。丙型肝炎病毒已经进化出一种或多种 急性加重期抑制宿主保护性免疫反应的策略 感染；从而促进病毒持久性的发展。我们有 确定了丙型肝炎病毒核心蛋白的一些重要功能特性。 这些包括对许多细胞启动子的跨调控作用， 调节细胞生长，在细胞程序性死亡中起抑制作用 (细胞凋亡)在一定条件下，未能诱导出强烈的细胞毒作用 免疫动物的T淋巴细胞反应。虽然所有这些功能 活动已经确立，在我们的理解上存在严重差距 核心蛋白发挥这些功能的机制。把这些放在一起 观察提供了一个令人信服的理由来关注和设计研究，这将 加深我们对细胞靶点和分子机制的理解 与丙型肝炎病毒核心蛋白的功能效应有关。这项研究 建议的目的是：(1)鉴定和鉴定核心蛋白 相互作用的细胞因子，(2)表征核心蛋白的作用机制 以及(3)确定核心蛋白对细胞凋亡的影响。 MHC-II类抗原表达。丙型肝炎病毒基因1a的核心蛋白是 慢性丙型肝炎患者的主要基因型别 美国，将在本研究中使用。拟议研究的结果 将扩大我们对核心蛋白分子机制的理解 并可能导致干预策略或 设计合适的抗丙型肝炎病毒感染的治疗方案。

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an association between hepatocellular carcinoma (HCC) and HCV infection has been noted. HCV has evolved one or more strategies to suppress the host protective immune responses during acute infection; thereby facilitating the development ofviral persistence. We have identified a number of important functional properties of the HCV core protein. These include a trans-regulatory role on a number of cellular promoters, regulation of cell growth, an inhibitory role in programmed cell death (apoptosis) under certain conditions, and failure to induce a strong cytotoxic T lymphocyte response in immunized animals. While all of these functional activities are well established, there are critical gaps in our understanding of the mechanisms by which core protein exerts these functions. Together these observations provide a compelling reason to focus and design studies which will further our understanding of the cellular targets and molecular mechanisms associated with the functional effects of HCV core protein. This research proposal is designed to: (1) identify and characterize the core protein interacting cellular factors, (2) characterize the mechanism of core protein mediated apoptotic inhibition, and (3) determine the effect of core protein on MHC class II antigen expression. The core protein from HCV genotype la, one of the predominant genotypes seen in patients with chronic HCV infection in the United States, will be used in this study. The results from the proposed study will extend our understanding of the molecular mechanisms of core protein mediated functional activities and may lead to intervention strategies or the design of appropriate therapeutic modalities against HCV infection.