IDENTIFYING THE MAJOR TISSUE RESERVOIRS IN SIV/SHIV INFECTED MACAQUES

识别 SIV/SHIV 感染猕猴的主要组织储存库

• 批准号: 7716274
• 负责人: Bapi Pahar
• 金额: $ 6.46万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716274
• 关键词: Acquired Immunodeficiency Syndrome; Anti-Retroviral Agents; Brain; CD4 Positive T Lymphocytes; Cells; Computer Retrieval of Information on Scientific Projects Database; Funding; Generations; Grant; HIV; HIV-1; Helper-Inducer T-Lymphocyte; Immune; Individual; Infection; Institution; Interruption; Intestines; Lymphoid; Macaca; Macaca mulatta; Modeling; Organ; Pathogenesis; Plasma; Research; Research Personnel; Resources; Role; SIV encephalitis; Source; Spleen; Study models; Systemic infection; Thymus Gland; Time; Tissues; Treatment Protocols; United States National Institutes of Health; Vaccines; Viral; Viral Load result; Viremia; Virus; antiretroviral therapy; design; lymph nodes; macrophage; vaccine efficacy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eradication of HIV-1 from an infected individual cannot be achieved by current usage of antiretroviral therapy regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy for a long time and are able to replenish systemic infection upon interruption of the treatment. Simian immune deficiency virus-rhesus macaque models of AIDS are a useful model for studying HIV pathogenesis and vaccine efficacy. We have used this model to explore the possible role of viral reservoirs in macaques that control viral replication with those that have persistently high viremia in plasma. The existence of actively replicating viruses in tissues correlates with plasma viral load. Similarly more latently infected cells were detected in macaques with a high plasma viral load. Lymph nodes were found to be the major tissue reservoir of virus followed by spleen, and intestinal tissues. Persistently infected cells in brain and thymus were detected in macaques with SIV-encephalitis. Therefore, anti-retroviral therapy should be designed in such a way that it can target infected cells in secondary lymphoid organs and reduce the generation of latently and persistently infected cells. T helper cells and macrophages were found to be the major cells that harbor persistently and latently infected cells, thus a vaccine or antiretroviral therapy should be specifically designed to protect these cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目前使用的抗逆转录病毒治疗方案无法从感染者体内根除 HIV-1。感染早期建立的病毒库在很长一段时间内不受抗逆转录病毒治疗的影响，并且在治疗中断后能够补充全身感染。艾滋病猴免疫缺陷病毒-恒河猴模型是研究艾滋病毒发病机制和疫苗功效的有用模型。我们使用这个模型来探索病毒库在猕猴中的可能作用，这些病毒库控制着血浆中持续高病毒血症的猕猴的病毒复制。组织中活跃复制病毒的存在与血浆病毒载量相关。同样，在血浆病毒载量较高的猕猴中也检测到了更多潜伏感染的细胞。淋巴结被发现是病毒的主要组织储存库，其次是脾脏和肠组织。在患有 SIV 脑炎的猕猴中检测到大脑和胸腺中持续感染的细胞。因此，抗逆转录病毒治疗的设计应能够针对次级淋巴器官中的感染细胞，并减少潜伏和持续感染细胞的产生。人们发现辅助性 T 细胞和巨噬细胞是持续和潜伏感染细胞的主要细胞，因此应专门设计疫苗或抗逆转录病毒疗法来保护这些细胞。