Viral Host Interactions in Hepatitis C

丙型肝炎中病毒宿主的相互作用

• 批准号: 7198097
• 负责人: David Richard Gretch
• 金额: $ 40.74万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198097
• 关键词: Address; Age; Alaska Native; Alcohol consumption; Antigens; Arctic Regions; Back; Cellular Immunity; Centers for Disease Control and Prevention (U.S.); Chronic; Chronic Hepatitis C; Clinical; Clinical Course of Disease; Cohort Studies; Collaborations; Data Analyses; Databases; Disease Outcome; Disease Progression; Enrollment; Evolution; Gender; Genotype; Goals; Grant; Hepatitis; Hepatitis C; Hepatitis C virus; Human; Immune response; Individual; Infection; Integration Host Factors; Investigation; Link; Liver diseases; Longitudinal Studies; Medical center; Molecular; Mutation; Native Americans; Outcome; Participant; Pathogenesis; Patients; Pattern; Play; RNA; Relative (related person); Research; Research Personnel; Resolution; Risk Factors; Role; Sampling; Serum; Specimen; Study Subject; Technology; Viral; Viremia; cohort; disease natural history; genetic evolution; human subject; liver biopsy; programs; prospective; response

DESCRIPTION (provided by applicant): Although the pathogenesis of chronic hepatitis C is poorly understood, recent studies implicate the dynamic interactions which occur between HCV and the infected host as key determinants of viral persistence and disease progression. Studies in humans indicate that genetic evolution of HCV to form viral quasispecies, and the strength of host CD4 and CDS response against HCV antigens are both critically linked to persistence of infection and progression of chronic liver disease. However, research confirming a direct interplay between HCV evolution and the immune responses of individual patients with specific outcomes needs to be performed. The overall goal of this proposal is to gain a better understanding of the pathogenesis of hepatitis C by investigating the relationships between HCV genetic evolution and host immune responses as they relate to resolution or persistence of infection and progression or non- progression of chronic liver disease. We will study subjects from the Alaska Native and American Indian cohort, taking advantage of a serum bank which dates back over 30 years and a large clinical and virological database compiled on approximately 1000 subjects over the past 8 years. HCV genetic evolution will be studied in the context of host immune responses in different clinical settings. Results from these studies will further our understanding of the mechanisms of HCV persistence and liver disease progression.

描述（由申请人提供）：尽管慢性丙型肝炎的发病机理尚不清楚，但最近的研究暗示了HCV和感染宿主之间发生的动态相互作用是病毒持续性和疾病进展的关键决定因素。人类的研究表明，HCV形成病毒的遗传进化，以及对HCV抗原的宿主CD4和CD反应的强度与慢性肝病的持续性和进展至关重要。然而，研究确认了HCV演化与具有特定结果的个体患者的免疫反应之间的直接相互作用。该提案的总体目标是通过研究HCV遗传进化与宿主免疫反应之间的关系，以更好地了解丙型肝炎的发病机理，因为它们与慢性肝病的分辨率或持续性或进展或非进展有关。我们将利用一家血清库来研究阿拉斯加原住民和美洲印第安人队列的受试者，该库的历史可以追溯到30多年，并且在过去的8年中大约1000名受试者汇编了大量的临床和病毒学数据库。 HCV遗传进化将在不同临床环境中的宿主免疫反应的背景下进行研究。这些研究的结果将进一步了解HCV持久性和肝病进展的机制。