Measuring the Latent Reservoir and Monitoring Eradication Strategies

测量潜在储库并监测根除策略

• 批准号: 8326895
• 负责人: DOUGLAS D RICHMAN
• 金额: $ 40.28万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-08 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326895
• 关键词: Address; Animal Model; Anti-Retroviral Agents; Biological Assay; Blood; Blood Volume; CD4 Positive T Lymphocytes; Cells; Characteristics; Clinical; DNA; Detection; Development; Flow Cytometry; HIV; HIV Infections; HIV-1; Human; In Vitro; Infection; Instruction; Intervention; Investigation; Latent Virus; Macaca; Measurement; Measures; Methods; Microfluidics; Modeling; Monitor; Natural History; Patients; Research Personnel; Research Project Grants; SIV; Sampling; Specimen; Study Subject; Technology; Testing; Tissues; Viral; Virus; antiretroviral therapy; collaboratory; improved; in vitro Model; in vivo; innovation; macrophage; monocyte; peripheral blood; programs; purge; simian human immunodeficiency virus; treatment effect; viral DNA

PROJECT SUMMARY (See instructions): The assays that have been applied to measure the latent reservoir in studies performed to date have been imprecise, in some cases non-specific, and in all cases near the threshold of detection for specimens obtained from subjects effectively treated with antiretroviral therapy. A successful Collaboratory effort to eradicate the latent reservoir must have assays available that can reliably quantify this reservoir and measure reductions in its size. In Project 4.1, superior assays in development for integrated viral DNA and for viral infectivity will be refined and validated for HIV, and then applied to both the SIV and RT-SHIV macaque models. They will then be applied to in vitro models of latency and to cells and tissues obtained from infected macaques and HIV-infected study subjects, as part of other Collaboratory research projects. Microfluidic applications to these assays will address the question of the representativeness of the proviral reservoir for replication-competent virus and try to explain some of the mechanisms for replication in competent virus. The presence of HIV DNA and infectivity in blood macrophages, as a potential reservoir, will also be examined. These studies to improve measurements of the latent reservoir and interventions to purge it will involve close interactions and the exchange of methods and materials with several of the project and core Collaboratory investigators.

项目总结（见说明）： 在迄今为止进行的研究中，用于测量潜伏储库的检测方法不精确，在某些情况下是非特异性的，并且在所有情况下都接近从接受抗逆转录病毒治疗的受试者中获得的标本的检测阈值。一个成功的消除潜在水库的合作努力必须有可用的测定，可以可靠地量化这个水库， 测量其尺寸的减小。在项目4.1中，将对正在开发的用于整合病毒DNA和病毒感染性的上级检测方法进行改进并验证HIV，然后将其应用于SIV和RT-SHIV猕猴模型。然后，作为其他合作实验室研究项目的一部分，它们将被应用于潜伏期的体外模型以及从受感染的猕猴和艾滋病毒感染的研究对象中获得的细胞和组织。 微流体应用这些检测将解决问题的代表性的前病毒水库的复制能力的病毒，并试图解释一些机制的复制能力的病毒。还将检查血液巨噬细胞中HIV DNA的存在和感染性，作为潜在的储存库。这些研究旨在改进对潜在储层的测量和对其进行清除的干预措施，将涉及与几个项目和核心合作实验室调查人员的密切互动以及方法和材料的交流。