TRANSFORMATION OF HUMAN B LYMPHOCYTES BY EPSTEIN-BARR VIRUS

拟议的研究有其长期目标，阐明 EB病毒（EBV）对人类癌症的贡献， 它是相关联的。许多观察表明，EBV有助于 通过启动和维持人淋巴瘤细胞的增殖， B淋巴细胞感染两种病毒蛋白质， 这些事件是EB核抗原1型（EBNA-1）和潜伏性 膜蛋白1（LMP-1）。本供资期间 EBNA-1和LMP-1的生物化学性质和功能已经被 鉴定这些属性和功能将被阐明 在本申请中提出的研究中， 在本供资期间开发的化验和试剂。EBNA- 1是EB病毒基因组作为质粒复制所必需的， 增殖细胞。它支持质粒的机制 将建立复制。EBNA-1的连接功能 有助于EBNA-1的复制和转录的支持， 分析了假设这种连接功能有助于 将测试病毒基因组在增殖细胞中的分配。的 第二种蛋白质LMP-1被假设为癌基因， 其在质膜上的组成性信号传导。两者的作用 氨基末端和羧基末端的细胞质部分， 蛋白质在信号传导中的作用将被研究。这些关于个人的研究 EB病毒的转化基因将通过开发新的 从基因上分析EBV的方法， 特定病毒基因的研究可以很容易地扩展到 整个病毒的背景。

The proposed research has its long term goal elucidation of the contributions of Epstein-Barr virus (EBV) to the human cancers with which it is associated. Many observations indicated that EBV contributes to human lymphoid tumors by initiating and maintaining proliferation of the infected B-lymphocyte. Two of the viral proteins that appear essential for these events are Epstein-Barr nuclear antigen type 1 (EBNA-1) and latent membrane protein type 1 (LMP-1). During the current funding period biochemical properties and functions of EBNA-1 and LMP-1 have been identified. These properties and functions will be elucidated mechanistically in the research proposed in this application using many of the assays and reagents developed during the current funding period. EBNA- 1 is required for replication of EBV's genome as a plasmid in proliferating cells. The mechanism by which it supports plasmid replication will be established. The role that EBNA-1's linking function contributes to EBNA-1's support of replication and transcription will be analyzed. The hypothesis that this linking function contributes to the partitioning of viral genomes in proliferating cells will be tested. The second protein, LMP-1, has been hypothesize to behave as an oncogene by its constitutive signaling at the plasma membrane. The role of both the amino-terminal and carboxy-terminal cytoplasmic moieties of this onco- protein in signaling will be investigated. These studies on individual transforming genes of EBV will be complemented by the development of new methods to analyze EBV genetically so that insights gained from the study of specific viral genes can be extended readily to their study in the context of the whole virus.