TRANSFORMATION OF HUMAN B LYMPHOCYTES BY EPSTEIN-BARR VIRUS

拟议的研究有其长期目标，即阐明 爱泼斯坦-巴尔病毒在人类癌症中的作用 它是关联的。许多观察表明，EBV有助于 人类淋巴样肿瘤通过启动和维持细胞的增殖 感染的B淋巴细胞。两种病毒蛋白，它们似乎对 这些事件是爱泼斯坦-巴尔核抗原1型(EBNA-1)和潜伏的 膜蛋白1(LMP-1)。在本供资期间 EBNA-1和LMP-1的生化性质和功能 已确认身份。这些属性和功能将被阐明 在这一应用中提出的研究中机械地使用了许多 化验和试剂是在本供资期间开发的。EBNA- 1是EBV基因组复制所必需的 正在增殖的细胞。它支持质粒的机制 将建立复制。EBNA-1‘S连接功能的作用 有助于EBNA-1的S对复制和转录的支持 分析过了。假设此链接函数对 将测试病毒基因组在增殖细胞中的分割。这个 第二种蛋白质LMP-1被认为是一种癌基因，通过 它在质膜上的构成信号。两者的作用都是 该瘤细胞的氨基末端和羧基末端的胞质部分 将对信号中的蛋白质进行研究。这些关于个体的研究 EBV的转化基因将被新的发展所补充 从基因上分析EBV的方法，以便从研究中获得见解 可以很容易地扩展到它们的研究中 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.