HEPATITIS C VIRUS REPLICATION AND LIVER INJURY

丙型肝炎病毒复制和肝损伤

• 批准号: 6770044
• 负责人: NELSON FAUSTO
• 金额: $ 82.52万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6770044
• 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（改编自应用程序）：丙型肝炎是一种新兴的 具有重大公共卫生意义的传染病。大约2%的 美国和欧洲的人口慢性感染丙型肝炎 病毒（HCV）。尽管HCV的研究取得了重大进展， 基因组及其编码的蛋白质，HCV机制的基本方面 发病机制仍然知之甚少。 其中一个主要困难是 缺乏足够的组织培养来研究相互作用 丙型肝炎病毒和肝细胞的天然宿主。此外， HCV感染者中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。本申请旨在研究 一种新的组织培养中HCV的复制和肝细胞损伤 系统的人胎肝细胞（HFH）以及在人类宿主。是 假设通过凋亡杀死细胞，保留允许细胞 其中病毒持续存在并且细胞因子信号传导的激活是事件 在HCV感染中发生，并可被病毒，肝细胞， 作为其天然宿主或通过病毒与宿主细胞之间的相互作用。 的 应用程序由3个项目和2个核心组成。项目1建议分析 丙型肝炎病毒的复制及其诱导细胞凋亡的机制 用全长HCV RNA或3 '缺失病毒转染作为对照， 以及在感染患者血清的HFH培养物中。项目2将使用cDNA 基因芯片对HFH中的基因表达进行全面分析 用全长和突变型HCV RNA转染，并研究其作用 干扰素的浓度。 项目3将调查 丙型肝炎病毒复制、准种进化和丙型肝炎疾病之间的关系 在阿拉斯加土著美国人（ANA队列）人群中， 血清、肝活组织检查以及临床和流行病学数据已被 收集。

项目成果

Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma.

• 发表时间: 2003-02
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Maria W. Smith;Zhaoxia N Yue;G. Geiss;Natalya Y. Sadovnikova;V. Carter;L. Boix;C. Lázaro;G. B. Rosenberg;Roger E Bumgarner;N. Fausto;J. Bruix;M. Katze

Risk of end-stage liver disease, hepatocellular carcinoma, and liver-related death by fibrosis stage in the hepatitis C Alaska Cohort.

• DOI: 10.1002/hep.29115
• 发表时间: 2017-07
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Bruden DJT;McMahon BJ;Townshend-Bulson L;Gounder P;Gove J;Plotnik J;Homan C;Hewitt A;Barbour Y;Spradling PR;Simons BC;McArdle S;Bruce M
• 通讯作者: Bruce M

Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells.

• DOI: 10.1186/1743-422x-2-89
• 发表时间: 2005-12-02
• 期刊: Virology journal
• 影响因子: 4.8
• 作者: Plumlee CR;Lazaro CA;Fausto N;Polyak SJ
• 通讯作者: Polyak SJ

Genetic diversity of near genome-wide hepatitis C virus sequences during chronic infection: evidence for protein structural conservation over time.

• DOI: 10.1371/journal.pone.0019562
• 发表时间: 2011-05-05
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Li H;Hughes AL;Bano N;McArdle S;Livingston S;Deubner H;McMahon BJ;Townshend-Bulson L;McMahan R;Rosen HR;Gretch DR
• 通讯作者: Gretch DR