PATHOGENESIS OF EPSTEIN-BARR VIRUS INFECTION

爱泼斯坦-巴尔病毒感染的发病机制

• 批准号: 8357905
• 负责人: Frederick C. Wang
• 金额: $ 6.84万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357905
• 关键词: Acquired Immunodeficiency Syndrome; Alanine; Blood; Cells; Cytotoxic T-Lymphocytes; EBNA-1 immune evasion; EBV-associated disease; EBV-associated malignancy; Epstein-Barr Virus Infections; Epstein-Barr pathogenesis; Funding; Genes; Glycine; Goals; Grant; Human Herpesvirus 4; Immune response; Individual; Infection; National Center for Research Resources; New England; Peptides; Phase; Primates; Principal Investigator; Process; Research; Research Infrastructure; Resources; Source; T-Lymphocyte; Therapeutic; United States National Institutes of Health; Viral Genes; Viral Proteins; base; cost; infected B cell; killings; persistent EBV infection; prevent; therapy development; tool; virus episome maintenance

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pathogenesis of Epstein-Barr Virus Infection The overall goal of our research is to better understand the pathogenesis of Epstein-Barr virus (EBV) infection in order to develop therapies that can reduce, control, or prevent EBV-associated diseases. EBNA-1 is an EBV protein important for the maintenance of the virus episome. EBNA-1 is expressed in all phases of EBV infection, is one of only a few viral genes expressed by infected B cells circulating in the blood of persistently infected hosts, and is the gene most consistently expressed in EBV associated malignancies. EBNA-1 specific cytotoxic T cells are present in persistently EBV infected individuals, but these T cells are unable to effectively kill EBV infected cells due in part to an inhibitory effect of the EBNA-1 glycine-alanine repeat (GAR) domain that prevents appropriate processing and presentation of EBNA-1 peptides to T cells. This application focuses on the importance of EBNA-1 for persistent EBV infection, the importance of EBNA-1 immune evasion for persistent infection, and the possibility of manipulating the EBNA-1 immune response as a therapeutic tool against EBV-associated malignancies. AIDS related.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 EB 病毒感染的发病机制 我们研究的总体目标是更好地了解 Epstein-Barr 病毒 (EBV) 感染的发病机制，以便开发能够减少、控制或预防 EBV 相关疾病的疗法。 EBNA-1 是一种 EBV 蛋白，对于维持病毒附加体很重要。 EBNA-1 在 EBV 感染的所有阶段都表达，是持续感染宿主血液中循环的受感染 B 细胞表达的少数病毒基因之一，也是 EBV 相关恶性肿瘤中表达最一致的基因。 EBNA-1 特异性细胞毒性 T 细胞存在于持续 EBV 感染的个体中，但这些 T 细胞无法有效杀死 EBV 感染的细胞，部分原因是 EBNA-1 甘氨酸-丙氨酸重复 (GAR) 结构域的抑制作用阻止了适当的治疗。 EBNA-1 肽的加工和呈递给 T 细胞。本申请重点关注 EBNA-1 对于持续性 EBV 感染的重要性、EBNA-1 免疫逃避对于持续性感染的重要性，以及操纵 EBNA-1 免疫反应作为针对 EBV 相关恶性肿瘤的治疗工具的可能性。 艾滋病相关。