Anitbody and saliva-mediated enhancement of epithelial cell infection by EBV

爱泼斯坦-巴尔病毒(EBV)是一种经口腔传播的人类疱疹病毒，其存活率超过90%。 成年人口的比例。大多数感染是无症状的，但可能与长期携带有关 随着淋巴系和上皮性恶性肿瘤的发展。频度和攻击性 其中，合并感染人类免疫缺陷病毒(HIV)的人增加了。近几年来 对EBV在其人类宿主中持续存在的生命周期进行了重新评估，并重新进行了 评价口咽上皮细胞在其维持中所起的中心作用。我们的长期计划 目标是了解靶向这种组织所涉及的参数。我们和其他人最近描述了 体内环境可以通过两种方式影响上皮细胞感染，这两种情况都意味着 主要的包膜糖蛋白gp350/220是将病毒与其B细胞上的CD21受体结合所必需的 不仅对于感染上皮细胞来说是可有可无的，而且还会干扰这一过程。我们的工作 表明对gp350/220的抗体，可能在艾滋病毒阳性个体中发现的高水平， 增强上皮细胞感染。我们假设gp350/220的抗体修补了病毒中的蛋白质。 包膜，以便于更多的相关病毒蛋白进入上皮细胞表面。我们的直接客户 目标是检验这一假设，确定病毒生命周期中的哪些步骤受到影响，并探索 HIV感染者唾液对病毒复制的影响。有四个具体目标。第一 目的评价HIV感染者唾液中抗体水平及其对上皮细胞的作用 感染。第二个目标是使用BAG技术制造缺乏gp350/220的重组病毒。这个 第三个目标是使用这种病毒和gp350/220抗体来确定上皮性感染的步骤是什么。 增强版。该方法将使用对分离细胞的实时聚合酶链式反应分析来跟踪病毒进入 穿透到原子核。第四个目标将使用微阵列技术来确定细胞内信号 事件会受到影响，如果它们影响复制的早期步骤。高患病率和高负荷率 HIV感染者中的EBV与口咽部肿瘤发病率的升高有关。我们的目标是 了解影响病毒复制的因素，以便评估风险并制定策略 避开它。

Epstein-Barr virus (EBV) is an orally-transmitted human herpesvirus that persists in more than ninety percent of the adult population. A majority of infections are asymptomatic but long term carriage can be associated with development of malignancies of both lymphoid and epithelial origin. The frequency and aggressiveness of these increase in individuals co-infected with the human immunodeficiency virus (HIV). In recent years there has been a reevaluation of the life cycle of persistence of EBV in its human host and a renewed appreciation of the central role that epithelial cells in the oropharynx play in its maintenance. Our long term goals are to understand the parameters involved in targeting this tissue. We and others recently described two ways in which the environment in vivo can influence epithelial infection, in both cases implying that the major envelope glycoprotein gp350/220, which is required to attach virus to its receptor CD21 on a B cell, is not only dispensable for infection of an epithelial cell, but also interferes with the process. Our work indicates that antibodies to gp350/220, which may be found at high levels in HIV-positive individuals, enhance epithelial cell infection. We hypothesize that antibodies to gp350/220 patch the protein in the virus envelope to facilitate access of more relevant virus proteins to the epithelial cell surface. Our immediate goals are to test this hypothesis, to determine what steps in the virus life cycle are impacted and to explore the effect of saliva from HIV infected individuals on virus replication. There are four specific aims. The first aim will evaluate the levels and contribution of antibodies in saliva of HIV infected individuals to epithelial cell infection. The second aim will use BAG technology to make recombinant viruses that lack gp350/220. The third aim will use this virus and antibodies to gp350/220 to determine what steps in epithelial infection are enhanced. The approach will be to use real time PCR analysis of fractionated cells to follow virus entry through into the nucleus. The fourth aim will use microarray technology to determine if intracellular signaling events are impacted and if they influence these early steps in replication. The high prevalence and loads of EBV in HIV infected individuals correlate with elevated incidence of oropharygeal tumors. Our goal is to understand the factors that influence virus replication in order to estimate risk and develop strategies to avoid it.