PATHOGENESIS OF EPSTEIN-BARR VIRUS INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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，以便开发能够减少、控制或预防EBV相关疾病的治疗方法。EBNA-1是一种EBV蛋白，对病毒Episome的维持很重要。EBNA-1在EBV感染的各个阶段都有表达，是在持续感染宿主的血液中循环的少数受感染B细胞表达的病毒基因之一，也是EBV相关恶性肿瘤中表达最稳定的基因。EBNA-1特异性细胞毒T细胞存在于持续感染EBV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EBNA-1肽的适当处理和呈递给T细胞。这项应用着重于EBNA-1对持续EBV感染的重要性，EBNA-1免疫逃避对持续感染的重要性，以及操纵EBNA-1免疫反应作为治疗EBV相关恶性肿瘤的工具的可能性。与艾滋病有关。

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.