TRANSFORMATION OF HUMAN B LYMPHOCYTES BY EPSTEIN-BARR VIRUS

爱泼斯坦-巴尔病毒对人 B 淋巴细胞的转化

• 批准号: 6590250
• 负责人: WILLIAM M. SUGDEN
• 金额: $ 18.34万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6590250
• 关键词: B lymphocyte; Epstein Barr virus; athymic mouse; cell growth regulation; cell line; cell transformation; gene expression; genetic transcription; human subject; leukocyte activation /transformation; lymphocyte proliferation; oncogenes; oncoproteins; phlebotomy; viral carcinogenesis; virus genetics; virus protein; virus replication

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.

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 人类淋巴肿瘤通过启动和维持增殖 感染的B淋巴细胞。两种病毒蛋白对于 这些事件是 Epstein-Barr 核抗原 1 型 (EBNA-1) 和潜在的 1 型膜蛋白 (LMP-1)。在当前资助期内 EBNA-1 和 LMP-1 的生化特性和功能已被 确定。这些属性和功能将得到阐明 在本申请提出的研究中机械地使用了许多 当前资助期间开发的检测方法和试剂。 EBNA- 1 是 EBV 基因组作为质粒复制所必需的 增殖细胞。支持质粒的机制 将建立复制。 EBNA-1的连接功能的作用 有助于 EBNA-1 支持复制和转录 分析了。假设该连接功能有助于 将测试增殖细胞中病毒基因组的划分。这 第二种蛋白质 LMP-1 被假设为癌基因 它在质膜上的组成型信号传导。两者的作用 该肿瘤的氨基末端和羧基末端细胞质部分 将研究信号传导中的蛋白质。这些研究针对个人 EBV 的转化基因将通过新的开发得到补充 对 EBV 进行基因分析的方法，以便从研究中获得见解 特定病毒基因的研究可以很容易地扩展到他们的研究中 整个病毒的背景。