REGULATION OF THE EBV LYTIC SWITCH GENE BZLF1

EB病毒(Epstein-Barr Virus，EBV)是一种嗜淋巴的人类疱疹病毒。 传染性单核细胞增多症的病原体，并与 随着几种人类癌症的发展。像其他疱疹病毒一样， EB病毒可确定为裂解性感染或潜伏性感染。建议数 研究涉及表征EBV裂解周期的调节。 基因BZLF1，已被证明是重要的诱导。 整个裂解瀑布。这些研究的长远目标是 了解EBV裂解周期的诱导机制 体内控制，以及这些机制对病毒的重要性 在宿主体内生存。对裂解诱导的适当调节可能会 对细胞间的传播和EBV的永生都很重要 被感染的细胞。这项建议的具体目的是1)分析 选定的BZLF1启动子和基因突变 病毒基因组。选定的突变将由同源基因 重组，以及对诱导裂解周期的影响， 永生化细胞系的形成和传染性将被研究。 2)BZLF1基因诱导效率的鉴定 潜伏感染的细胞。将使用现场技术来比较 BZLF1基因产物与其他裂解抗原的融合表达 细胞可诱导基因决定是否诱导裂解 周期被特异性地阻断在BZLF1基因的表达上。 申请者已经制定了这项计划，目标是成为 建立了独立的爱泼斯坦-巴尔病毒调查员。这个 申请者将100%致力于建议的研究 这项奖励的期限，以最大限度地实现潜力 这个目标。赞助商的实验室是根据以下条件选择的 科学价值、热情、EBV知识、可获得性 资源，对申请者的敬业精神；此外还有强大的 该机构的病毒学家和免疫学家的社区 专业知识对申请者的科学发展将是无价的。

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.