EBV GENOME EXPRESSION--LOCALIZATION OF SPECIFIC FUNCTION

EB病毒(EBV)使B细胞永生，与人类 恶性肿瘤包括伯基特淋巴瘤，鼻咽癌， 中国人胃癌、何杰金氏病和淋巴增生性疾病 免疫抑制患者如艾滋病患者与器官和骨髓 移植病人。EBV原发感染可能导致传染性 年轻人的单核细胞增多症。原发感染导致增殖性 感染的B细胞扩增。其次是建立 EBV基因组驻留在静止的B细胞中的终生持久性。裂解 病毒复制发生在口咽部，并导致病毒脱落到 唾液。 在潜伏感染的患者中可以看到不同的EBV潜伏基因表达模式 静息B细胞和EBV相关肿瘤中。此应用程序用于 可能调节这些表达模式并有助于 EBV发病机制的不同方面。EBV复制对于病毒来说是必要的 传播和Zta是EBV裂解循环的关键调节因子。Zta不仅 调节EBV裂解DNA复制，但也可能影响 潜伏感染。具体目标是：(目标1)。描述…的角色 Zta在EB病毒复制中的起源为裂解复制，orilyt。转染法 检测将被用来分析Zta在复制形成中的作用 间隔，分析Zta转录的相对贡献 和复制活动与orilyt激活和与Zta介导的相关 调节细胞周期对Zta复制功能的影响。(目标2)。评估 JAK-STAT信号通路在EB病毒调控中的作用 潜伏期基因在体内的表达与肿瘤的发生。统计数据调节 的单个EBV潜伏期启动子将在瞬时检测中进行检测。这个 激活的STATS和Zta表达在维持EBV阳性中的作用 上皮性肿瘤细胞株在培养过程中将受到追寻和负调控 将按统计数据检查EBV裂解周期。(目标3)。EBNA-1在 EBV潜伏期基因表达的调节将被评估。

Epstein-Barr virus (EBV) immortalizes B cells and is associated with human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's disease and lymphoproliferative disease in immunosuppressed patients such as AIDS patients and organ and bone marrow transplant patients. Primary infection by EBV may cause infectious mononucleosis in young adults. Primary infection leads to a proliferative expansion of the infected B cells. This is followed by the establishment of life-long persistence in which the EBV genome resides in resting B cells. Lytic viral replication occurs in the oropharynx and results in virus shedding into the saliva. Different patterns of EBV latency gene expression are seen in latently infected resting B cells and in EBV associated tumors. This application addresses factors that may regulate these expression patterns and contribute to the different aspects of EBV pathogenesis. EBV replication is necessary for virus spread and Zta is a key regulator of the EBV lytic cycle. Zta not only regulates EBV lytic DNA replication but may also influence the maintainance of latent infection. The Specific Aims are: (Aim 1). To characterize the role of Zta in replication of the EBV origin of lytic replication, orilyt. Transfection assays will be used to analyse the role of Zta in the formation of replication compartments, to analyze the relative contributions of Zta's transcriptional and replication activities to orilyt activation and to relate Zta mediated regulation of the cell cycle to Zta replication function. (Aim 2). To evaluate the contribution of the JAK-STAT signaling pathway to the regulation of EBV latency gene expression in in vivo latency and tumorigenesis. STAT regulation of individual EBV latency promoters will be examined in transient assays. The role of activated STATs and Zta expression in the maintainance of EBV positive epithelial tumor cell lines in culture will be pursued and negative regulation of the EBV lytic cycle by STATs will be examined. (Aim 3). A role for EBNA-1 in the regulation of EBV latency gene expression will be evaluated.