Consequences of acute HIV infection on the EBV-specific immunity

急性 HIV 感染对 EBV 特异性免疫的影响

• 批准号: 7878524
• 负责人: CHRISTIAN BRANDER
• 金额: $ 22.04万
• 依托单位: FUNDACIO IRSICAIXA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-03 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878524
• 关键词: Acute; Address; Affect; Authorization documentation; Biopsy; Blood specimen; Boston; CD4 Positive T Lymphocytes; Cell Line; Cells; Cellular Immunity; Chronic; Clinical; Data; Defect; Development; Disclosure; Disease; Epitopes; Event; Face; Failure; Gene Expression; General Hospitals; Geographic Locations; HIV; HIV Infections; Herpesviridae; Herpesviridae Infections; Human; Human Herpesvirus 8; Human Resources; Immune; Immune response; Immunity; Impairment; Individual; Infection; Instruction; Knowledge; Last Name; Link; Lymphoma; Lytic; Massachusetts; Molecular Profiling; Monitor; Names; Oral cavity; Pattern; Peru; Population; Principal Investigator; Printing; Recovery; Registries; Research Personnel; Research Project Grants; Role; Sampling; Site; South America; Staging; T cell response; T-Lymphocyte; Therapeutic Intervention; Time; Tonsil; Viral; Viral Antigens; Viral Genes; Viremia; Virus; Virus Shedding; base; cohort; disorder control; high risk; human embryonic stem cell; insight; memory CD4 T lymphocyte; migration; peripheral blood; programs; prospective

The development of EBV and KSHV driven lymphomas in the oral cavity is a serious clinical issue in HIV infected subjects. Despite its relatively frequent occurrence in some geographic areas, including South America, little is known how the herpesvirus specific immunity or lack thereof, is associated with disease control. In particular essentially no data exist regarding the impact of acute HIV infection on the pre-existing EBV and KSHV specific immunity and its consequences for later disease manifestation. This lack of knowledge is largely due to logistical difficulties to examine the herpesvirus-specific cellular immune response in individuals immediately before and after HIV infection. The availability of a closely monitored cohort of individuals at high risk for HIV infection, combined with detailed immune analyses would overcome this important gap in our understanding how immune events during acute HIV infection predispose individuals for long-term control of herpesviral infections. The present study aims to establish such as cohort and to assess EBV and KSHV specific immune responses on a single epitope level before and after HIV infection. Using sensitive and multi-parameter flow-cytometryapproaches the proposed studies will help to assess whether HIV infection leads to a complete loss of some herpesvirus specific T cell responses or whether HIV infection leads to a possibly transient functional silencing of these reactivities. Comparing blood samples to cells obtained form tonsilar biopsies, the studies will address whether the changes in the peripheral blood are a consequence of profound immune aberrations in the tonsil, an important site of viral replication for orally transmitted viruses. The tonsil samples will also allow to perform viral gene expression analyses in projects 2 and 3 of this proposal, helping to link detected immune responses to the presence or absence of viral antigens in this site. Together, the analyses in project 4 will provide unique insight into the early immune events that surround acute HIV infection and that may determine herpesvirus control in these co-infected subjects. Performing these analyses in a untreated HIV cohort in Lima, Peru will also deepen our understanding of cellular immunity against herpesvirus infections common to this geographic area and frequently associated with disease manifestation in the oral cavity.

口腔中EBV和KSHV驱动的淋巴瘤的发展是HIV感染受试者的严重临床问题。尽管在某些地理区域（包括南方）发生了相对频繁的发生 美国鲜为人知的疱疹病毒特异性免疫或缺乏疾病控制是如何与疾病控制有关的。特别是根本上没有关于急性HIV感染对现有的影响的数据 EBV和KSHV特异性免疫及其对以后疾病表现的后果。缺乏知识在很大程度上是由于后勤困难检查了疱疹病毒特异性的细胞免疫 艾滋病毒感染前后的个体的反应。密切监测的艾滋病毒感染风险高风险的个体的可用性将克服详细的免疫分析 在我们理解急性HIV感染期间的免疫事件中，这一重要差距使人长期控制疱疹病毒感染。本研究旨在建立诸如队列 并在HIV感染前后在单个表位水平上评估EBV和KSHV特异性免疫反应。使用敏感和多参数流量计学应用程序拟议的研究将有助于评估HIV感染是否会导致某些疱疹病毒特异性T细胞反应的完全丧失，或者HIV感染是否导致这些反应激素的可能短暂的功能沉默。将血液样本与获得的细胞形成tonsilar活检，研究将解决周围血液中的变化是否是扁桃体中严重免疫像差的结果，扁桃体是口服传播病毒的重要部位。扁桃体样品还将允许在该提案的项目2和3中进行病毒基因表达分析，有助于将检测到的免疫反应与该站点中病毒抗原的存在或不存在联系起来。总之，项目4中的分析将为围绕急性HIV感染的早期免疫事件提供独特的见解，这可能决定这些事件 共同感染的受试者。秘鲁在利马的未经处理的艾滋病毒队列中进行这些分析，还将加深我们对该地理区域常见的疱疹病毒感染的细胞免疫力的理解和 通常与口腔中的疾病表现相关。