Oral immune responses in human and simian herpesvirus infection

人类和猿猴疱疹病毒感染的口腔免疫反应

• 批准号: 6657063
• 负责人: David T Scadden
• 金额: $ 20.92万
• 依托单位: PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657063
• 关键词: Epstein Barr virus; Gammaherpesvirinae; Herpesviridae disease; Macaca mulatta; communicable disease transmission; cytotoxic T lymphocyte; epitope mapping; human herpesvirus 8; human immunodeficiency virus; human subject; mucosal immunity; oral mucosa; patient oriented research; simian immunodeficiency virus; virus diseases; virus virus interaction

Oral immune response to viral infections have not been well- characterized despite the potential importance as an early line of defense. In particular, herpesviruses implicated in HIV related opportunistic malignancies and HIV itself have potential oral mucosal modes of transmission and yet oral immunity against them remains unexplored. This proposal seeks to characterize oral mucosal immune responses in humans to KSHV, EBV and HIV comparing them to the more well defined immune responses against these viruses in the blood. In addition, we will user a non-human primate model of EBV infection to perform detailed analysis to perform detailed analysis of oral mucosal immunity at distinct sites and time points in rhesus macaques exposed to the rhesus lymphocryptovirus (LCV), a herpesvirus that is closely related to EBV. These experiments will compare immunocompetent animals with those immunodeficient through SIV infection. The specific goals of this project are to: 1. establish the targets of the anti-KSHV specific CTL response in KSHV infected individuals, leading to the further characterization of minimal CTL epitopes derived from KSHV. Using similar methods we will identify CTL responses to rhesus LCV, the similar herpesvirus homolog of EBV in rhesus macaques. 2. Compare the magnitude and target specificity of CTL responses to rhesus LCV and SIV in the oral cavity and peripheral blood of SIV naive and SIV-infected rhesus macaques, 3. Define human CTL responses to HIV, EBV and KSHV infection in the oral cavity compared with blood. We will correlate the magnitude, specificity and kinetics of these responses with 1) disease progression and 2) anti-retroviral treatment. The results from these studies will guide the development of vaccination strategies to induce mucosal immunity in the oral cavity against important pathogens in HIV disease.

尽管潜在的重要性是早期的防御线，但对病毒感染的口服免疫反应尚未得到很好的特征。特别是，与HIV相关的机会性恶性肿瘤和艾滋病毒本身有关的疱疹病毒具有潜在的口腔传播粘膜模式，但对它们的口服免疫力仍未得到探索。该提案试图表征人类对KSHV，EBV和HIV的口服粘膜免疫反应，将其与血液中针对这些病毒的更明确的免疫反应进行了比较。此外，我们将使用EBV感染的非人类灵长类动物模型进行详细的分析，以对暴露于恒河猴淋巴细胞病毒（LCV）（LCV）的恒河猴（LCV）的不同部位和时间点的口服粘膜免疫进行详细分析，与EBV密切相关的疱疹病毒。这些实验将通过SIV感染将免疫能力动物与那些免疫缺陷进行比较。该项目的具体目标是：1。在受KSHV感染的个体中建立抗KSHV特异性CTL响应的目标，从而进一步表征来自KSHV的最小CTL表位。使用类似的方法，我们将识别对恒河猴的恒河猴的响应，这是恒河猕猴中类似的EBV疱疹病毒同源物。 2。比较口腔中对恒河猴LCV和SIV的幅度和目标特异性，以及SIV NAIVE和SIV感染的Rhesus Macaques的外周血，3。与血液相比，定义人类CTL对HIV，EBV和KSHV感染的反应。我们将将这些反应的大小，特异性和动力学与1）疾病进展和2）抗逆转录病毒治疗相关联。这些研究的结果将指导疫苗接种策略的发展，以诱导口腔中的粘膜免疫，以抗HIV疾病中重要的病原体。