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: 7479325
• 负责人: CHRISTIAN BRANDER
• 金额: $ 27.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 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/7479325
• 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 4; Human Herpesvirus 8; Human Resources; Immune; Immune response; Immunity; Impairment; Individual; Infection; Instruction; Knowledge; Last Name; Link; Lymphoma; Lytic; Massachusetts; Molecular Profiling; Monitor; Names; Numbers; Oral cavity; Pattern; Personal Satisfaction; Peru; Population; Principal Investigator; Printing; Recovery; Registries; Research Personnel; Research Project Grants; Risk; Role; Sampling; Simplexvirus; Site; South America; Staging; T-Lymphocyte; Therapeutic Intervention; Time; Tonsil; Viral; Viral Antigens; Viremia; Virus; Virus Shedding; base; cohort; disorder control; human embryonic stem cell; insight; memory CD4 T lymphocyte; migration; peripheral blood; programs; prospective; response

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.

EBV 和 KSHV 驱动的口腔淋巴瘤的发展对于 HIV 感染者来说是一个严重的临床问题。尽管它在一些地理区域相对频繁地发生，包括南部 在美国，人们对疱疹病毒特异性免疫力或缺乏特异性免疫力与疾病控制之间的关系知之甚少。特别是，基本上不存在关于急性艾滋病毒感染对已有疾病的影响的数据。 EBV 和 KSHV 特异性免疫及其对后期疾病表现的影响。这种知识的缺乏主要是由于检查疱疹病毒特异性细胞免疫的后勤困难 HIV 感染前后个体的反应。对艾滋病毒感染高危人群进行密切监测，并结合详细的免疫分析，将克服这一问题。 我们理解急性艾滋病毒感染期间的免疫事件如何使个体易于长期控制疱疹病毒感染，这是我们理解的一个重要差距。本研究旨在建立诸如队列 并评估 HIV 感染前后单表位水平上的 EBV 和 KSHV 特异性免疫反应。使用灵敏的多参数流式细胞术方法，拟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 细胞反应完全丧失，或者 HIV 感染是否导致这些反应性可能短暂的功能性沉默。通过将血液样本与扁桃体活检获得的细胞进行比较，这些研究将解决外周血的变化是否是扁桃体严重免疫畸变的结果，扁桃体是口腔传播病毒的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，有助于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，并可能决定这些地区的疱疹病毒控制。 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了解， 通常与口腔疾病表现相关。