ASSESSMENT OF ALVEOLAR MACROPHAGES AS A RESERVOIR FOR HIV

肺泡巨噬细胞作为 HIV 储存库的评估

• 批准号: 7603533
• 负责人: Lisa M Frenkel
• 金额: $ 0.17万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603533
• 关键词: Adult; Alveolar Macrophages; Anti-HIV Agents; Blood; Blood Cells; Cells; Child; Clinical; Computer Retrieval of Information on Scientific Projects Database; Funding; Future; Grant; HIV therapy; HIV-1; Highly Active Antiretroviral Therapy; Infection; Injection of therapeutic agent; Institution; Location; Longevity; Lung; Patients; Pharmaceutical Preparations; Pharmacotherapy; Quality of life; Research; Research Personnel; Resources; Site; Source; Sputum; Treatment Protocols; United States National Institutes of Health; Virus; Virus Replication; Visit; drug resistant virus; genetic analysis; improved; macrophage

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. Highly active antiretroviral therapy (HAART) for HIV-1 infection has significantly improved the lifespan and quality of life of HIV-infected children and adults. However, even when replication of the virus is halted by HAART, there are reservoirs where the virus hides and will begin to replicate once drug-therapy is stopped. Additionally, drug-resistant virus from continued replication threatens the longevity of HIV therapy. A significant portion of patients continue to have replication despite therapy that keeps the virus suppressed in the blood. The location or locations in the body where this replication persists is unknown. One possibility is that the replication persists in the specific lung cells, called macrophages. Macrophages are less susceptible to some of the HIV-drugs because the cells do not convert the drug to the active form or the cells require a much higher concentration of the drug to stop replication. Additionally, it is difficult to get enough of the drug to the lung macrophages. In order to determine if lung macrophages are both a reservoir and a site of persistent replication of HIV-1 infection, we are collecting lung macrophages by induced sputum yearly and extra blood at clinical visits to compare the virus in the blood cells to the virus in the lung cells in 20 children on HAART. Through detailed genetic analyses, we will be able to determine if the lung cells are a reservoir of HIV-injection and if lung macrophages are a site of persistent replication. If replication continues in the lung macrophages when suppressed in the blood, then future studies will be proposed to evaluate the activity of different anti-HIV drug regimens in the lung macrophages.

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。 HIV-1感染的高度活性抗逆转录病毒疗法（HAART）显着改善了HIV感染的儿童和成人的寿命和生活质量。 但是，即使HAART将病毒的复制暂停，也有一些储层，一旦停止了药物疗法，病毒就可以隐藏并开始复制。此外，持续复制的耐药病毒威胁着艾滋病毒疗法的寿命。 尽管治疗使病毒抑制血液中的病毒，但很大一部分患者仍继续复制。 该复制持续的人体中的位置或位置未知。 一种可能性是，复制持续存在于特定的肺部细胞中，称为巨噬细胞。 巨噬细胞不太容易受到某些HIV-药物的影响，因为细胞不会将药物转化为活性形式，或者细胞需要更高浓度的药物才能停止复制。 此外，很难将足够的药物吸入肺巨噬细胞。 为了确定HIV-1感染的肺巨噬细胞是否既是储层和持续复制的位点，我们每年通过诱导的痰液收集肺巨噬细胞，而在临床就诊时进行额外的血液，以比较Haart的20名儿童的血细胞中的血细胞病毒与血液细胞的血细胞与病毒。 通过详细的遗传分析，我们将能够确定肺部细胞是否是HIV注入的储层，以及肺巨噬细胞是否是持续复制的部位。 如果在血液中抑制肺巨噬细胞中的复制继续，则将提出未来的研究来评估肺巨噬细胞中不同抗HIV药物方案的活性。