EBV GENOME EXPRESSION--LOCALIZATION OF SPECIFIC FUNCTION

EB病毒（EBV）使B细胞永生化，并与人类免疫缺陷病毒（HIV）相关。 恶性肿瘤包括伯基特淋巴瘤，鼻咽癌， 胃癌、霍奇金病和淋巴组织增生性疾病 免疫抑制患者，如艾滋病患者和器官和骨髓 移植患者EBV的原发性感染可引起传染性 年轻人单核细胞增多症。原发性感染会导致 感染的B细胞的扩增。其次是建立 EBV基因组存在于静息B细胞中的终生持久性。裂解 病毒复制发生在口咽部， 唾液 在潜伏感染者中观察到EBV潜伏基因表达的不同模式， 静息B细胞和EBV相关肿瘤中。本申请涉及 这些因子可能调节这些表达模式，并有助于 EBV发病机制的不同方面。EB病毒复制是病毒复制所必需的。 传播和Zta是EBV裂解周期的关键调节因子。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EBV裂解性复制起点的复制中，orilyt。转染 分析将用于分析Zta在复制形成中的作用。 区室，以分析Zta的转录的相对贡献， 和复制活动orilyt激活和相关Zta介导的 细胞周期对Zta复制功能的调节。(Aim 2）。评价 JAK-STAT信号通路对EBV调控的作用 潜伏基因表达在体内潜伏期和肿瘤发生中的作用。STAT调节 将在瞬时测定中检查单个EBV潜伏期启动子。的 激活的STATs和Zta表达在EB病毒感染中的作用 上皮肿瘤细胞株在培养中将受到负调控 将检查STAT对EBV裂解周期的影响。(Aim 3）。EBNA-1的作用 评价EBV潜伏基因表达的调节。

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.