INITIATION OF CELL INFECTION WITH EPSTEIN-BARR VIRUS

EB病毒（EBV）是一种人类疱疹病毒，其建立慢性疱疹病毒感染。 携带者几乎占全世界人口的100%。 它作为一种与传染性疾病相关的病原体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 免疫抑制性淋巴瘤，鼻咽癌，T细胞 恶性肿瘤和霍奇金病。 目前的发病机制模型 表明EB病毒在上皮组织中高效复制 在口咽部并在B淋巴细胞中建立潜伏期。病毒然后贩运 当它进入人体并周期性地脱落时， 感染者的唾液中。这项工作的长期目标是 了解EBV感染两种靶细胞的第一步， 这对病毒在宿主内和宿主之间的传播至关重要。的 该应用程序的直接目标是使用最近开发的 获得EBV突变体的技术，以研究已知或 在这个过程中的推定EBV包膜蛋白。突变的表型 将在体外原代B淋巴细胞和SV 40中检查病毒 已用所述B细胞转染的转化上皮细胞系 EB病毒受体。 将在体内检查突变病毒的表型 在CB。17只scid/scid免疫缺陷小鼠移植人 淋巴上皮组织有三个具体目标。一是 检测缺失gp 85复合物中蛋白质表达的影响 病毒穿透细胞的能力。其他点突变 将评价gp 85对复合物完整性的影响 使用分离表达的重组蛋白;那些不 干扰复合物形成将被构建到病毒中， 功能分析第二个目的是检查病毒的表型 gp 110的表达缺失，其是HSV-gB的EBV同源物。第三 目的是确定是否有四个剩余的潜在病毒粒子 膜蛋白是病毒复制所必需的， 每个人的位置证明是这样的。

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.