PATHOGENESIS, CHRONICITY, AND MUTATIONS OF HEPATITIS B

乙型肝炎的发病机制、慢性性和突变

• 批准号: 2837703
• 负责人: CHIAHO SHIH
• 金额: $ 26.27万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-23 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2837703
• 关键词: T cell receptor; chronic disease /disorder; clinical research; gene mutation; hepatitis B; hepatitis B antigens; hepatitis B virus group; hepatocellular carcinoma; host organism interaction; human subject; immunopathology; major histocompatibility complex; receptor binding; tissue /cell culture; virus cytopathogenic effect; virus genetics

DESCRIPTION: Chronic infection with human hepatitis B virus (HBV) leads to liver damage, cirrhosis and liver cancer. The applicant's goal is to elucidate the molecular basis of pathogenicity, chronicity, and clearance of HBV infection. Although chronicity has been attributed to host factors, such as the immune response, viral factors per se have remained largely uninvestigated. The applicant's preliminary results suggest that in chronic carriers and hepatoma patients HBV-acquired mutations may cause antigenic changes that lead to escape from the immune system. They propose to test more directly and definitively the hypothesis that accumulation of certain viral mutations is crucial for the persistence of pathogenic HBV during its long term interaction with the host. The immunopathological interactions between certain HBV core antigen mutants and the host will be studied via assays for peptide-major histocompatibility complex (peptide-MHC) binding, antigen processing and T cell receptor recognition. Specifically, three aims are proposed: Aim 1) to test the hypothesis that certain core antigen mutations affect MHC-peptide binding; Aim 2) to test the hypothesis that aberrant HBV core antigen processing could result from immune escape mutants; Aim 3) to test the hypothesis that certain core antigen mutations affect TCR peptide-MHC recognition. This last aim may be expanded to include the examination of TCR-antagonistic or agonistic mutant core antigens.

描述：慢性感染人类乙型肝炎病毒 (HBV) 会导致 肝损伤、肝硬化和肝癌。 申请人的目标是 阐明致病性、慢性性和清除的分子基础 乙型肝炎病毒感染。 尽管慢性归因于宿主因素， 例如免疫反应，病毒因素本身在很大程度上仍然存在 未经调查。 申请人的初步结果表明，在慢性 携带者和肝癌患者 HBV 获得性突变可能引起抗原性 导致逃避免疫系统的变化。 他们建议测试 更直接和明确的假设是，某些物质的积累 病毒突变对于致病性乙型肝炎病毒在其传播过程中的持续存在至关重要。 与主人长期互动。 免疫病理学相互作用 某些 HBV 核心抗原突变体与宿主之间的关系将通过以下方式进行研究 肽-主要组织相容性复合物（肽-MHC）结合测定， 抗原加工和 T 细胞受体识别。 具体来说，三 提出目标： 目标 1) 检验某些核心抗原的假设 突变影响 MHC 肽结合；目标 2) 检验假设 乙肝病毒核心抗原加工异常可能是免疫逃逸造成的 突变体；目标 3) 检验某些核心抗原突变的假设 影响TCR肽-MHC识别。 最后一个目标可能会扩大到 包括 TCR 拮抗或激动突变核心的检查 抗原。