INITIATION OF CELL INFECTION WITH EPSTEIN-BARR VIRUS

用 Epstein-Barr 病毒启动细胞感染

• 批准号: 2061298
• 负责人: Lindsey M. Hutt-Fletcher
• 金额: $ 18.5万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2061298
• 关键词: B lymphocyte; Epstein Barr virus; SCID mouse; epithelium; gene deletion mutation; hematopoietic tissue transplantation; human subject; human tissue; laboratory rabbit; latent virus infection; membrane proteins; point mutation; tissue /cell culture; transfection; virus envelope; virus infection mechanism; virus protein; virus receptors; virus replication

Epstein-Barr virus (EBV) is a human herpesvirus that establishes a chronic carrier state in almost one hundred per cent of the population world-wide. It has considerable importance as a pathogen associated with infectious mononucleosis, oral hairy leukoplakia, Burkitt's lymphoma, immunoblastic lymphomas of the immunosuppressed, nasopharyngeal carcinoma, T cell malignancy and Hodgkin's disease. A current model of pathogenesis suggests that EBV replicates productively in epithelial tissue of the oropharynx and establishes latency in B lymphocytes. Virus then trafficks between the two cell types as it enters the body and is periodically shed in saliva of infected individuals. The long term objective of this work is to understand the first steps in infection of both target cells of EBV which are critical to spread of virus within and between hosts. The immediate goals of this application are to use recently developed techniques for deriving EBV mutants to investigate the roles of known or putative EBV envelope proteins in the process. The phenotypes of mutated virus will be examined in vitro in primary B lymphocytes and in an SV40 transformed epithelial cell line that has been transfected with the B cell receptor for EBV. Phenotypes of mutated viruses will be examined in vivo in CB. 17 scid/scid immunodeficient mice engrafted with human lymphoepithelial tissue. There are three specific aims. The first is to examine the effects of deleting expression of proteins in the gp85 complex on the ability of virus to penetrate cells. Additional point mutations in gp85 will be evaluated for their effects on the integrity of the complex using recombinant proteins expressed in isolation; those that do not interfere with complex formation will then be built into virus for further functional analyses. The second aim is to examine the phenotype of virus deleted for expression of gp110, the EBV homologue of HSV-gB. The third aim is to determine whether or not four remaining potential virion membrane proteins are essential for virus replication, and to examine the location of each that proves to be so.

爱泼斯坦-巴尔病毒(EBV)是一种人类疱疹病毒，它建立了一种慢性 世界上几乎100%的人口都是携带者。 作为一种与传染性疾病相关的病原体，它具有相当重要的意义。 单核细胞增多症、口腔毛状白斑、伯基特淋巴瘤、免疫母细胞瘤 免疫抑制的淋巴瘤，鼻咽癌，T细胞 恶性肿瘤和霍奇金氏病。一种目前的发病机制模型 提示EB病毒可在鸡上皮组织中高效复制 口咽，并在B淋巴细胞中建立潜伏期。然后病毒就会传播 两种类型的细胞之间的关系，因为它进入人体并定期脱落 在感染者的唾液中。这项工作的长期目标是 了解EBV两种靶细胞感染的第一步 它们对病毒在主机内和主机之间的传播至关重要。这个 这个应用程序的近期目标是使用最近开发的 用于获得EBV突变体以研究已知或 在这一过程中可能存在EBV包膜蛋白。突变的表型 病毒将在原代B淋巴细胞和SV40中进行体外检测 转导B细胞的转化上皮细胞系 EB病毒受体。变异病毒的表型将在体内进行检测 单位为CB。17只接种人的SCID/SCID免疫缺陷小鼠 淋巴上皮组织。有三个具体目标。第一个是 检测gp85复合体中蛋白质表达缺失的影响 病毒穿透细胞的能力。中的其他点突变 将评估gp85对综合体完整性的影响。 使用分离表达的重组蛋白；那些不 干扰复杂的形成将被构建到病毒中，以便进一步 功能分析。第二个目的是检查病毒的表型。 HSV-GB的EBV同源物gp110的表达缺失。第三 目的是确定是否还有四个潜在的病毒粒子 膜蛋白对病毒复制是必不可少的，并检查 每个人的位置都证明是这样的。