HOST IMMUNITY TO EBV INFECTION IN VITRO AND IN VIVO

宿主对 EBV 感染的体外和体内免疫力

• 批准号: 2060763
• 负责人: David A. Thorley-Lawson
• 金额: $ 27.97万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2060763
• 关键词: B lymphocyte; Burkitt's lymphoma; Epstein Barr virus; biological products; genetic manipulation; genetic regulatory element; genetic transcription; glycoproteins; host organism interaction; human subject; hybridomas; immunity; in situ hybridization; ionomycin; laboratory mouse; lymphocyte proliferation; messenger RNA; microorganism immunology; molecular cloning; monoclonal antibody; mononucleosis; nasopharyngeal neoplasms; nucleic acid sequence; oncogenic virus; radioimmunoassay; tissue /cell culture; tumor antigens; viral carcinogenesis; virus antigen; virus cytopathogenic effect; virus infection mechanism

Epstein-Barr virus (EBV) is a persistent herpesvirus that is carried latently and reactivates, usually without harm to the infected individual. EBV infects and "immortalizes" or "growth transforms" normal resting human B cells in vitro driving them to become latently infected proliferating lymphoblasts. The virus also plays a central role in several human diseases, including several B cell neoplasias. The goal of this proposal will be to investigate the relationship between normal B cell biology and the establishment of a latent, persistent infection by Epstein-Barr virus. Specifically, we will address two aspects of this relationship. First, we will undertake a detailed analysis of how a model B cell activation gene (Blast-1) is regulated. Blast-1 is an adhesion molecule, restricted in its expression to lymphoid and myeloid cells, that is upregulated by EBV infection. We will map the minimal promoter and the sequences responsible for tissue specific expression. We will establish the relative roles of increased transcription and mRNA stabilization in activation by EBV. Regulatory elements so defined will be mapped. The mechanism will then be compared to that of other known activators including IL-4, PMA, IL-lb and ionomycin. Second, we will study the relationship between the form of the persistent viral genome and the differentiation stage of the infected cell. Specifically, we will investigate the role of cellular activation stage in determining whether the virus persists as an episome or integrated. The viral sequences involved in episomal amplification will be investigated. Previously identified integration sites will be cloned and sequenced to investigate the mechanism of integration. Lastly, tumor cell lines will be tested for the presence of integrated EBV genomes by the fluorescence in situ hybridization technique to provide a definitive answer as to whether such sequences are or are not present.

Epstein-Barr病毒（EBV）是一种持续的疱疹病毒 延伸并重新激活，通常不会对感染者造成伤害 个人。 EBV感染和“永生”或“增长变化”正常 静止的人类B细胞在体外驱动它们成为潜在感染的 增殖的淋巴细胞。 该病毒在 几种人类疾病，包括几种B细胞肿瘤。 目标 该建议将是调查正常B之间的关系 细胞生物学和通过 爱泼斯坦 - 巴尔病毒。 具体来说，我们将解决这两个方面 关系。 首先，我们将对如何进行详细分析 B细胞激活基因（BLAST-1）受调节。 Blast-1是一个 粘附分子，其表达限制为淋巴样和髓样 EBV感染的细胞上调。 我们将绘制最小的 启动子和负责组织特异性表达的序列。 我们将建立增加转录和mRNA的相对作用 EBV激活的稳定。 如此定义的监管元素将 被映射。 然后将将该机制与其他已知的机制进行比较 包括IL-4，PMA，IL-LB和离子霉素在内的激活剂。 第二，我们会的 研究持续性病毒基因组形式之间的关系 以及受感染细胞的分化阶段。 具体来说，我们 将研究细胞激活阶段在确定的作用 无论该病毒是否一直持续为沿着综合体或整合。 病毒 将研究参与偶发放大的序列。 先前确定的集成位点将被克隆并测序 研究整合的机理。 最后，肿瘤细胞系将 可以通过荧光测试是否存在综合的EBV基因组 原位杂交技术，以提供明确的答案 这些序列是否存在。