REGULATION OF THE EBV LYTIC SWITCH GENE BZLF1

Epstein-Barr病毒（EBV）是一种人类嗜淋巴细胞疱疹病毒， 传染性单核细胞增多症的病原体，并与 几种人类癌症的发展。与其他疱疹病毒一样， EB病毒可以建立溶解性或潜伏性感染。拟议 研究涉及表征EBV裂解周期的调节 基因BZLF 1，已被证明是重要的诱导， 整个裂解级联。这些研究的长期目标是 了解EBV裂解周期诱导的机制， 控制在体内，这些机制的重要性，以病毒 在宿主中生存。适当调节裂解诱导可能 对于EB病毒的细胞间传播和永生化都很重要 被感染的细胞本建议的具体目标是：（1）分析 选择的BZLF 1启动子和基因突变的背景下， 病毒基因组选择的突变将通过同源的 重组，以及对诱导裂解周期的影响， 将研究永生化细胞系的形成和感染性。 2)BZLF 1基因在大肠杆菌中诱导效率的表征 潜伏感染细胞原位技术将用于比较 BZLF 1基因产物与其它裂解抗原和与 细胞诱导基因，以确定是否诱导裂解 在BZLF 1基因表达时特异性阻断循环。 申请人制定本提案的目的是成为 EB病毒的独立研究者。的 申请人将投入100%的努力，为拟议的研究， 此奖项的持续时间，以最大限度地发挥潜力， 这个目标。申办方实验室的选择基于 科学价值，热情，EBV知识，可用性 资源，并致力于申请人;此外，还有一个强大的 这个机构的病毒学家和免疫学家社区， 专业知识对申请人的科学发展将是非常宝贵的。

Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus which is the etiologic agent of infectious mononucleosis, and is closely associated with the development of several human cancers. Like Other herpesviruses, EBV can establish either a lytic or latent infection. The proposed research involves characterizing the regulation of the EBV lytic cycle gene BZLF1, which has been shown to be important for induction of the entire lytic cascade. The long-term objectives of these studies are to understand the mechanisms whereby induction of the lytic cycle of EBV is controlled in vivo, and the importance of these mechanisms to viral survival in the host. Proper regulation of lytic induction is likely to be important both for cell-to-cell spread and for immortalization of EBV infected cells. The specific aims of this proposal are 1) Analysis of selected BZLF1 promoter and gene mutations within the context of the viral genome. Selected mutations will be made by homologous recombination, and the effects on induction of the lytic cycle, the formation of immortalized cell lines, and infectivity will be studied. 2) Characterization of the efficiency of induction of the BZLF1 gene in latently infected cells. In situ techniques will be used to compare expression of the BZLF1 gene product with other lytic antigens and with cellular inducible genes to determine whether induction of the lytic cycle is blocked specifically at BZLF1 gene expression. The applicant has developed this proposal with an objective to become an established, independent investigator of the Epstein-Barr virus. The applicant will devote 100% effort to the proposed research for the duration of this award, in order to maximize the potential to realize this objective. The sponsor's laboratory was chosen on the basis of scientific merit, enthusiasm, knowledge of EBV, availability of resources, and dedication to the applicant; in addition there is a strong Community of virologists and immunologists at this institution whose expertise will be invaluable to the applicant's scientific development.