ROLE OF RAZ IN EBV LIFE CYCLE

EB病毒（Epstein-Barr virus，EBV）是一种嗜B型人类疱疹病毒 淋巴细胞和上皮细胞钟。EBV引起传染性单核细胞增多症， 淋巴增生性疾病并与几种恶性肿瘤有关， 包括伯基特淋巴瘤、鼻咽癌和霍奇金淋巴瘤 疾病EBV在B淋巴细胞中建立潜伏感染， 无限期细胞增殖然而，潜伏感染的细胞可以 在体外通过诱导关键的 立即早期基因BZLF 1（Z），它导致从潜伏期转换到 溶细胞复制最近，帕加诺博士的实验室发现了一种 编码的Z调节基因产物称为RAZ。RAZ是一种嵌合形式， BRLF 1和BZLF 1基因产物，并作为反式显性阻遏物。在 在体外，RAZ与Z异二聚体，它是相关的，并导致Z- 诱导的反式激活和再激活级联反应。这项建议是 RAZ的发现及其初步表征的后续行动， 重点介绍了这种新型嵌合蛋白的生物学作用， 其对原发感染、转化和病毒的作用机制 重新激活RAZ基因敲除突变体病毒的制备与筛选 本文提出原发感染中突变病毒的表征 效率、转化效率和病毒再活化也是 该项目将使我们能够清楚地确定 RAZ在其实际病毒背景中的作用。 了解RAZ功能将 加深我们对EBV基因调控的理解，最终可能导致 控制和治疗EBV相关疾病。

Epstein-Barr virus (EBV) is a human herpesvirus with tropism for B lymphocytes and epithelial bells. EBV causes infectious mononucleosis and lymphoproliferative disease and is associated with several malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease. EBV establishes a latent infection in B lymphocytes and causes indefinite cell proliferation. However, the latently infected cells can be reactivated in vitro by induction of the expression of the key immediate-early gene, BZLF1 (Z), which leads to switch from latency to cytolytic replication. Recently, Dr. Pagano's laboratory found a virally encoded Z-modulatory gene product termed RAZ. RAZ is a chimeric form of BRLF1 and BZLF1 gene products, and acts as a transdominant repressor. In vitro, RAZ heterodimerizes with Z, to which it is related, and causes Z- induced transactivation and the reactivation cascade. This proposal is a follow-up to the discovery of RAZ and its initial characterization that focuses on the biologic role of this novel chimeric protein and the mechanism of its effects on primary infection, transformation, and viral reactivation. The generation and selection of RAZ knock-out mutant virus is proposed. Characterization of the mutant virus in primary infection efficiency, transformation efficiency and viral reactivation are also proposed in detail This project will enable us to determine clearly the role of RAZ in its actual viral context. Understanding RAZ function will deepen our understanding of EBV gene regulation and eventually may lead to control and treatment of EBV-associated disease.