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

抗体和唾液介导的 EBV 上皮细胞感染增强

• 批准号: 7487007
• 负责人: Lindsey M. Hutt-Fletcher
• 金额: $ 28.98万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-20 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487007
• 关键词: Address; Adult; Affect; Age; Antibodies; B-Lymphocytes; Binding; Biology; Cell Nucleus; Cell surface; Cells; Childhood; Complement; Complement 3d Receptors; Cytomegalovirus; DNA Viruses; Development; Disease; Environment; Epithelial; Epithelial Cells; Epstein-Barr Virus Infections; Event; Frequencies; Glycoproteins; Goals; HIV; Hairy Leukoplakia; Herpesviridae; High Prevalence; Human; Human Herpesvirus 4; Human Papillomavirus; In Vitro; Incidence; Individual; Infection; Infectious Mononucleosis; Life Cycle Stages; Lymphoid; Maintenance; Malignant Neoplasms; Microarray Analysis; Mouth Neoplasms; NIH Program Announcements; Oral; Oral health; Oropharyngeal; Other Finding; Play; Polymerase Chain Reaction; Population; Process; Risk Estimate; Role; Saliva; Signal Pathway; Signal Transduction; Simplexvirus; Technology; Testing; Time; Tissues; Viral Proteins; Virus; Virus Diseases; Virus Replication; Work; in vivo; patched protein; receptor; recombinant virus; saliva mediated; tumor; tumor growth; viral DNA; virus envelope

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.

EB病毒（EBV）是一种经口传播的人类疱疹病毒， 的成年人口。大多数感染是无症状的，但长期携带可能与 伴随淋巴和上皮来源的恶性肿瘤的发展。频率和攻击性 其中，同时感染人类免疫缺陷病毒（艾滋病毒）的人数有所增加。近年来 人们重新评估了EB病毒在人类宿主中持续存在的生命周期， 对口咽上皮细胞在其维持中发挥的核心作用的认识。我们的长期 目标是了解靶向该组织所涉及的参数。我们和其他人最近描述了 体内环境可以影响上皮感染的两种方式，在这两种情况下， 主要包膜糖蛋白gp 350/220是将病毒附着到B细胞上的受体CD 21上所必需的， 这不仅会导致上皮细胞的感染，而且会干扰该过程。我们的工作 表明gp 350/220的抗体，在HIV阳性个体中可能以高水平存在， 增强上皮细胞感染。我们假设gp 350/220的抗体修补了病毒中的蛋白质 包膜，以促进更多相关病毒蛋白进入上皮细胞表面。我们眼前的 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感染者的唾液对病毒复制的影响。有四个具体目标。第一 目的是评估HIV感染者唾液中抗体的水平和对上皮细胞的贡献， 感染第二个目标将使用BAG技术制造缺乏gp 350/220的重组病毒。的 第三个目标将使用这种病毒和gp 350/220抗体来确定上皮感染的步骤 增强该方法将使用分级细胞的真实的时间PCR分析来跟踪病毒进入 进入细胞核。第四个目标将使用微阵列技术来确定细胞内信号是否 事件是否会受到影响，以及它们是否会影响复制中的这些早期步骤。高流行率和负荷 HIV感染者中的EBV与卵巢癌的发病率升高相关。我们的目标是 了解影响病毒复制的因素，以估计风险并制定策略， 避免它。