EBV GENOME EXPRESSION--LOCALIZATION OF SPECIFIC FUNCTION

EB病毒(Epstein-Barr Virus，EBV)是引起嗜异性粒细胞阳性的病原体 传染性单核细胞增多症与两种恶性疾病有关 Burkitts淋巴瘤，一种常见于热带非洲的儿童癌症 东南部发病率最高的鼻咽癌 亚洲。EBV基因组阳性淋巴瘤在免疫抑制中的表现 在这个国家，患者也成为一个令人担忧的问题。通过 美国80%的青春期人口EBV血清阳性 病毒在成年后一直潜伏在B淋巴细胞中。 了解控制建立潜伏期和 病毒裂解周期的诱导应该与阐明 EBV在这些肿瘤中的作用及对免疫抑制的处理 患者(肿瘤科患者、骨髓、心脏和肾脏移植 患者和艾滋病患者)，其中重新激活的感染是经常发生的 很复杂。 该项目的长期目标是描述和理解 EBV基因组表达调控的多种机制 在潜伏状态的维持期间，在从潜伏期和 在裂解周期的不同时间阶段。最初的目标 是1.鉴定调节序列(或多肽)，它们是 负责从潜伏期到裂解周期的转换。角色 相关的NotI和PstI重复基因及其他激活元件 将对特定早期抗原和病毒衣壳抗原基因进行评估 在DNA转染和显微注射系统中。此外，该综合体 上游启动子来自裂解表达的Noti重复基因 与外源检测基因连锁的杂合重组载体 将被用来评估回文特征是否 为它作为推动者的力量做出贡献，并检查它的能力 对TPA和其他诱导剂做出反应。2.使用DNA转染法和 微量注射分析识别和定位额外EBV的基因 抗原，并检测与潜在调控片段的共转染 作为一种激活基因表达的手段，这些基因通常在 这个化验结果。3.作为识别特定病毒基因的一步 直接参与淋巴细胞永生化的一种尝试 从P3HR-1培养物中拯救重组转化病毒 显微注射P3HR-1缺失的DNA片段 与不朽的过程有关。

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.