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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 当前使用抗逆转录病毒疗法方案无法实现从感染者中消除HIV-1。长期以来，在感染期间早期建立的病毒储层不受抗逆转录病毒疗法的影响，并且能够在治疗中断后能够补充全身感染。艾滋病的猿猴免疫缺陷病毒震撼猕猴模型是研究HIV发病机理和疫苗功效的有用模型。我们已经使用该模型来探索病毒储层在猕猴中的可能作用，以控制病毒复制与血浆中持续高病毒血症的复制作用。组织中积极复制病毒的存在与血浆病毒载量相关。同样，在具有高血浆病毒载量的猕猴中检测到了更延迟感染的细胞。发现淋巴结是病毒的主要组织库，其次是脾脏和肠道组织。在SIV-脑膜炎的猕猴中检测到大脑和胸腺中持续感染的细胞。因此，应设计抗逆转录病毒疗法，以使其可以靶向次生淋巴器官中的受感染细胞并减少潜在的和持续感染的细胞的产生。发现T辅助细胞和巨噬细胞是持续和潜在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以保护这些细胞。