Functional Activities of HCV Core Protein

描述（由申请人提供）：丙型肝炎病毒（HCV）通常会引起 长期和持续性感染，以及肝细胞 已经注意到肝癌（HCC）和HCV感染。HCV已经进化出一种或多种 急性期抑制宿主保护性免疫反应的策略 感染;从而促进病毒持续性的发展。我们有 鉴定了HCV核心蛋白的许多重要功能特性。 这些包括对许多细胞启动子的反式调节作用， 调节细胞生长，在程序性细胞死亡中起抑制作用 （凋亡）在一定条件下，并未能诱导强细胞毒性 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，但我们的理解存在重大差距 核心蛋白发挥这些功能的机制。综合这些 观察提供了一个令人信服的理由，集中和设计的研究， 进一步了解细胞靶点和分子机制 与HCV核心蛋白的功能作用相关。本研究 该方案旨在：（1）鉴定和表征核心蛋白 相互作用的细胞因子，（2）表征核心蛋白的机制 介导的凋亡抑制，和（3）确定核心蛋白对细胞凋亡的影响。 MHC II类抗原表达。来自HCV基因型la的核心蛋白，其中一种是 慢性HCV感染患者中的主要基因型 美国，将用于本研究。拟议研究的结果 将扩展我们对核心蛋白分子机制的理解 介导的功能活动，并可能导致干预策略或 设计针对HCV感染的适当治疗方式。

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.