Consequences of acute HIV infection on the EBV-specific immunity

由EBV和KSHV引起的口腔淋巴瘤的发展是HIV感染者面临的严重临床问题。尽管它在包括南方在内的一些地理区域相对频繁地发生 在美国，人们几乎不知道疱疹病毒的特异性免疫或缺乏与疾病控制有关。特别是，基本上没有关于急性艾滋病毒感染对先前存在的 EBV和KSHV特异性免疫及其对以后疾病表现的影响。这种知识的缺乏在很大程度上是由于检查疱疹病毒特异性细胞免疫的后勤困难。 艾滋病病毒感染前后个体的反应。提供一组受到密切监测的艾滋病毒感染高危人群，结合详细的免疫分析，将克服 我们在理解急性艾滋病毒感染期间的免疫事件如何使个人易于长期控制疱疹病毒感染方面的这一重要差距。本研究旨在建立这样的队列 并在单个表位水平上评估HIV感染前后EBV和KSHV特异性免疫反应。使用灵敏和多参数的流式细胞术方法，建议的研究将有助于评估HIV感染是否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的可能的一过性功能性沉默。将血液样本与扁桃体活检获得的细胞进行比较，研究将探讨外周血液的变化是否是扁桃体深刻的免疫异常的结果，扁桃体是口腔传播病毒复制的重要部位。扁桃体样本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，帮助将检测到的免疫反应与该部位是否存在病毒抗原联系起来。总而言之，项目4中的分析将为急性HIV感染周围的早期免疫事件提供独特的见解，并可能决定这些患者的疱疹病毒控制。 共同感染的受试者。在秘鲁利马未经治疗的艾滋病毒队列中进行这些分析，也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的理解。 经常与口腔中的疾病表现有关。

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.