EBV GENOME EXPRESSION--LOCALIZATION OF SPECIFIC FUNCTION

EB病毒（EBV）是嗜异性阳性的病原体， 传染性单核细胞增多症与两种恶性疾病有关 伯基特淋巴瘤，一种常见于热带非洲的儿童癌症， 鼻咽癌在东南部发病率最高 亚洲 免疫抑制者EB病毒基因组阳性淋巴瘤的出现 病人也成为这个国家关注的一个原因。 通过 青春期80%的美国人口是EBV血清阳性， 病毒在整个成人生活中都以潜伏状态存在于B淋巴细胞中。 了解控制延迟建立的机制， 病毒裂解周期的诱导应该与阐明 EBV在这些肿瘤中的作用以及免疫抑制治疗的管理 患者（肿瘤患者、骨髓、心脏和肾脏移植 患者和艾滋病受害者），在这些地方， 并发症 该项目的长期目标是描述和理解 参与调节EBV基因组表达的各种机制 在维持潜伏状态期间，在从潜伏期诱导期间， 在溶解周期的不同时间阶段。 初始目标 为1.为了鉴定调控序列（或多肽）， 负责从潜伏期到裂解周期的转换。 的角色 相关NotI和PstI重复基因和其他元件的激活 将评估特异性早期抗原和病毒衣壳抗原基因的 DNA转染和显微注射系统。 此外，复杂 来自裂解表达的NotI重复基因的上游启动子将被 与杂合重组质粒中的异源测试基因连接 这些结构将用于评估回文特征是否 作为一个促进者，帮助其力量，并检查其能力， 对TPA和其他诱导物有反应。 2.利用DNA转染技术， 显微注射分析，以确定和映射其他EBV的基因 抗原并检查与潜在调控片段的共转染 作为一种激活基因表达的手段， 这个化验。 3.作为鉴定特定病毒基因的一步 直接参与淋巴细胞永生化，将尝试 从P3 HR-1培养物中拯救重组转化病毒， 显微注射P3 HR-1缺乏的DNA片段， 与永生化过程有关

Epstein-Barr Virus (EBV) is the causative agent of heterophile positive infectious mononucleosis and is associated with two malignant diseases Burkitts lymphoma, a childhood cancer common in tropical Africa and nasopharyngeal carcinoma which occurs in highest incidence in Southeast Asia. The appearance of EBV-genome positive lymphomas in immunosuppressed patients is also becoming a cause for concern in this country. By adolescence 80% of the U.S.A. population is sero-positive for EBV and the virus persists in a latent state in B-lymphocytes throughout adult life. An understanding of the mechanisms controlling establishment of latency and induction of the viral lytic cycle should be of relevance to elucidating the role of EBV in these tumors and to the management of immunosuppressed patients (oncology patients, bone marrow, heart and renal transplant patients and AIDS victims) where reactivated infections are a frequent complication. The long term objectives of the project are to describe and understand the various mechanisms involved in regulating the expression of the EBV genome during maintenance of the latent state, during induction from latency and during the different temporal stages of the lytic cycle. The initial goals are 1. To identify the regulatory sequences (or polypeptides) which are responsible for the conversion from latency to the lytic cycle. The roles of the related NotI and PstI repeat genes and other elements in activation of specific early antigen and virus capsid antigen genes will be evaluated in DNA transfection and microinjection systems. In addition, the complex upstream promoter from the lytically expressed NotI repeat gene will be linked to heterologous test genes in hybrid recombinant plasmid constructions which will be used to assess whether the palindromic features contribute to its strength as a promoter and to examine its ability to respond to TPA and other inducers. 2. To use DNA transfection and microinjection assays to identify and map the genes for additional EBV antigens and to examine co-transfection with potential regulatory fragments as a means of activating expression of genes which are normally silent in this assay. 3. As a step toward identifying the specific viral genes directly involved in lymphocyte immortalization an attempt will be made to rescue recombinant transforming virus from P3HR-1 cultures by microinjection of those DNA fragments that are lacking in P3HR-1 and are implicated in the immortalization process.