HEPATITIS C VIRUS REPLICATION AND LIVER INJURY

丙型肝炎病毒复制和肝损伤

• 批准号: 6659780
• 负责人: NELSON FAUSTO
• 金额: $ 80.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6659780
• 关键词: cellular pathology; cooperative study; hepatitis C; hepatitis C virus; liver cells; virus replication

DESCRIPTION (Adapted from application): Hepatitis C is an emerging infectious disease of major public health importance. Approximately 2% of the population of the USA and Europe are chronically infected with hepatitis C virus (HCV). Although major progress has been made in studies of the HCV genome and its encoded protein, basic aspects of the mechanisms of HCV pathogenesis are still poorly understood. One of the major difficulties has been the lack of an adequate tissue culture in which to study the interactions between HCV and hepatocytes, its natural host. Furthermore, the mechanisms of viral persistence and quasispecies evolution in HCV infected patients as well as the relationships between viral replication and disease progression remain to be determined. This application seeks to study the relationships between HCV replication and hepatocyte injury in a newly developed tissue culture system for human fetal hepatocytes (HFH) as well as in the human host. It is hypothesized that cell killing by apoptosis, preservation of permissive cells in which the virus persists and activation of cytokine signaling are events that occur in HCV infection and can be modified by the virus, the hepatocyte as its natural host or by interaction between virus and host cells. The application consists of 3 projects and 2 cores. Project 1 proposes to analyze HCV replication and the mechanisms of HCV-induced apoptosis in cultures transfected with full length HCV RNA or a 3'deleted virus used as control as well as in HFH cultures infected with patient sera. Project 2 will use cDNA microarrays to conduct a comprehensive analysis of gene expression in HFH transfected with full length and mutant HCV RNAs and investigate the effects of interferon on these cells. Project 3 will investigate the relationships between HCV replication, quasispecies evolution and hepatitis C disease progression in a population of Alaskan Native Americans (ANA cohort) from which serum, liver biopsies and clinical and epidemiological data have been collected.

描述(改编自应用)：丙型肝炎是一种新兴的 具有重大公共卫生重要性的传染病。约2%的 美国和欧洲的人口长期感染丙型肝炎 病毒(丙型肝炎病毒)。尽管对丙型肝炎病毒的研究已经取得了重大进展 基因组及其编码蛋白，丙型肝炎病毒发病机制的基本方面 其发病机制目前尚不清楚。其中一个主要的困难是 一直缺乏足够的组织培养来研究相互作用 在丙型肝炎病毒与其自然宿主肝细胞之间。此外，其作用机制也不同 丙型肝炎病毒感染者的病毒持久性和准种进化 由于病毒复制和疾病进展之间的关系仍然存在 待定。这个应用程序试图研究 新型组织培养中的丙型肝炎病毒复制与肝细胞损伤 人胎肝细胞(HFH)以及在人类宿主中的系统。它是 假设细胞通过凋亡来杀死，保存允许的细胞 其中病毒持续存在和细胞因子信号的激活是事件 出现在丙型肝炎病毒感染中，并可被病毒、肝细胞 作为其自然宿主或通过病毒与宿主细胞之间的相互作用。这个 应用程序由3个项目和2个核心组成。项目1建议分析 丙型肝炎病毒复制及其诱导细胞凋亡的机制 以丙型肝炎病毒全长RNA或3‘端缺失病毒为对照 在感染患者血清的HFH培养中也是如此。项目2将使用cDNA 微阵列用于全面分析HFH中的基因表达 转染人丙型肝炎病毒全长和突变型RNA的实验研究 干扰素对这些细胞的影响。项目3将调查这些关系 丙型肝炎病毒复制、准种进化与丙型肝炎 阿拉斯加土著美国人(ANA队列)人口的进展 哪些血清、肝活检以及临床和流行病学数据 收好了。