Immunopathogenesis of acute and early HIV infection

急性和早期艾滋病毒感染的免疫发病机制

• 批准号: 7901307
• 负责人: Fred T Valentine
• 金额: $ 43.7万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901307
• 关键词: Immunopathogenesis; acute; early; HIV; infection

DESCRIPTION (provided by applicant): The title of this Program Project application is: Immunopathogenesis of Acute and Early HIV Infection. The program will consist of 4 projects supported by 2 core facilities. The program also will be supported by the infrastructures of the immunology, virology and clinical support (biostatistics-epidemiology) cores of the NYU CFAR and will rely heavily on resources within the AIDS Clinical Trials Unit. The program will be highly integrated in that some investigators will be working on more than one of the projects, and experiments will be performed in different projects on samples obtained at the same time from the same patients to facilitate interpretation of the results. All results will be entered into a common data-base developed by Frontier Science. The overall question of why strong CD4 reactivity to HIV antigens is lost or is not induced in subjects in whom treatment is delayed will be addressed in different ways by each of the projects. Immune responses control almost all viral infections that are not lethal during the first few days, yet long-term effective immunological control of HIV occurs in a small minority of infected individuals. The mechanisms by which HIV blocks the establishment of effective immune responses are not clear, but must be operative at the earliest stages of the infection. These mechanisms may include malfunctioning of the antigen presentation process by dendritic cells, inappropriate hyperactivation of T cells and apoptosis, or deletion or unresponsiveness of CD4 clones responsive to HIV antigens. Long-term nonprogressors with a low viral load maintain lymphocyte proliferative responses (LPR) to HIV antigens, a memory response, whereas the majority of individuals with established infection lack strong LPR to HIV antigens even after suppression of viral load with antiretroviral therapy. Our hypothesis is that the failure to develop and maintain memory CD4 responses to HIV antigens is a pivotal pathologic process in HIV infection. This program will take advantage of the large numbers of acute and early HIV infections being identified at NYU/Bellevue and our affiliated hospitals, combined with the large numbers of similar individuals. (At present NYU/Bellevue is tied with UCSD for top enrollment into the ACTG study of primary HIV infection.) We also will follow the cohort of individuals who are at exceedingly high risk of acute infection for whom we will have viably frozen cells obtained prior to infection should it occur.

描述（由申请人提供）：该计划项目申请的标题是：急性和早期艾滋病毒感染的免疫发病机制。该计划将包括由 2 个核心设施支持的 4 个项目。该计划还将得到纽约大学 CFAR 的免疫学、病毒学和临床支持（生物统计学-流行病学）核心基础设施的支持，并将严重依赖艾滋病临床试验部门的资源。该计划将高度集成，因为一些研究人员将从事多个项目，并且将在不同的项目中对同一患者同时获得的样本进行实验，以方便对结果的解释。所有结果都将输入 Frontier Science 开发的通用数据库中。 每个项目将以不同的方式解决为什么延迟治疗的受试者对 HIV 抗原的强 CD4 反应性消失或未诱导的总体问题。 免疫反应控制了几乎所有在最初几天内不致命的病毒感染，但对艾滋病毒的长期有效免疫控制发生在少数感染者身上。 HIV 阻止有效免疫反应建立的机制尚不清楚，但必须在感染的最早阶段发挥作用。这些机制可能包括树突状细胞抗原呈递过程的故障、T细胞的过度激活和细胞凋亡、或者对HIV抗原有反应的CD4克隆的缺失或无反应。病毒载量低的长期非进展者维持对 HIV 抗原的淋巴细胞增殖反应（LPR），这是一种记忆反应，而大多数已确诊感染的个体即使在用抗逆转录病毒治疗抑制病毒载量后，也缺乏对 HIV 抗原的强 LPR。我们的假设是，未能形成和维持对 HIV 抗原的记忆 CD4 反应是 HIV 感染的关键病理过程。 该计划将利用纽约大学/贝尔维尤分校和我们附属医院发现的大量急性和早期艾滋病毒感染者，以及大量类似的个体。 （目前，纽约大学/贝尔维尤分校与加州大学圣地亚哥分校并列参与 ACTG 原发性 HIV 感染研究的顶尖入组人数。）我们还将跟踪急性感染风险极高的人群，我们将为他们提供事先获得的活冷冻细胞。如果发生感染。

项目成果

Natural history of HIV infected pediatric long-term or slow progressor population after the first decade of life.

生命第一个十年后感染艾滋病毒的儿童长期或缓慢进展人群的自然史。

• DOI: 10.1097/01.inf.0000254413.11246.e1
• 发表时间: 2007
• 期刊: The Pediatric infectious disease journal
• 作者: Ofori-Mante,JulianaA;Kaul,Aditya;Rigaud,Mona;Fidelia,Andre;Rochford,Gemma;Krasinski,Keith;Chandwani,Sulachni;Borkowsky,William
• 通讯作者: Borkowsky,William