PATHOGENESIS OF EPSTEIN-BARR VIRUS INFECTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 我们研究的总体目标是更好地了解EB病毒（EBV）感染的发病机制，以开发可以减少，控制或预防EBV相关疾病的疗法。EBNA-1是一种对维持病毒附加体很重要的EBV蛋白。 EBNA-1在EBV感染的所有阶段中表达，是由在持续感染宿主的血液中循环的感染的B细胞表达的仅有的几种病毒基因之一，并且是在EBV相关恶性肿瘤中最一致表达的基因。 EBNA-1特异性细胞毒性T细胞存在于持续性EBV感染的个体中，但这些T细胞不能有效地杀死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，其阻止EBNA-1肽向T细胞的适当加工和呈递。本申请的重点是EBNA-1对持续性EBV感染的重要性，EBNA-1免疫逃避对持续性感染的重要性，以及操纵EBNA-1免疫应答作为针对EBV相关恶性肿瘤的治疗工具的可能性。 艾滋病相关

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.