EFFECTS OF HIV AND CMV UPON THE ALVEOLAR MACROPHAGE

最近的发现清楚地表明，没有真正的“潜伏期”。 与艾滋病毒疾病有关，至少在严格意义上是这样 学期。活跃的病毒复制在整个过程中都在进行 临床无症状期，通常发生在最初 感染。这些发现使病毒本身很可能 在感染者的临床恶化中起着关键作用 个人的。体外和体内数据都证明了这种能力 感染并携带艾滋病毒的组织巨噬细胞的数量。这些细胞 既可以作为长期的流动水库，也可以作为传播 病毒，并作为一些主要临床症状的媒介 与晚期艾滋病毒疾病有关。已经有相当多的 推测它们在糖尿病的发病机制中起着关键作用。 艾滋病，尽管对其作用了解相对较少 在与艾滋病相关的机会性感染的发展中。 在肺的独特环境中，肺泡巨噬细胞 代表宿主细胞免疫反应的主要介体 抗肺部病原体，HIV感染细胞对 肺脏防御系统尤其相关。整体而言 这项研究计划的目的是描绘出这种机制 人类免疫缺陷病毒感染肺泡巨噬细胞的机制 最终导致机会主义的肺功能障碍 感染。这些机制既包括艾滋病毒对人类健康的影响 肺泡巨噬细胞的功能及其相互作用 在免疫受损的人中发现的艾滋病毒和其他病原体之间的关系 阿龙。关于肺泡巨噬细胞本身，这个项目 是专门针对理解失控的 HIV对肺泡巨噬细胞产生细胞因子的影响 感染及其病理生理后果。在这个范围内 项目中，我们还将讨论CMV的作用，这是另一种最常见的病毒 通常与艾滋病相关的肺防御机制受损。 肺泡巨噬细胞功能与感染的关系 卡氏假单胞菌和分枝杆菌也将在 计划中协作项目的上下文。我们的目标是 开发有关肺系统内手术动力学的数据 HIV感染者之间，两者之间的不同入侵 在这些生物体和宿主组织之间，在 足够的分子细节来实施特定的策略 旨在干扰这些破坏性的过程。一 提出了利用基因进行干预的具体策略 作为试剂和知识基础的产物的治疗 在此项目中生成。

Recent findings make it clear that there is no true "latency phase" associated with HIV disease, at least in the strict sense of the term. Active virus replication is ongoing throughout the long clinical asymptomatic period which typically follows initial infection. These findings make it likely that the virus itself plays a key role in the clinical deterioration of the infected individual. Both in vitro and in vivo data demonstrate the ability of tissue macrophages to be infected by and harbor HIV. These cells may serve both as long-lived mobile reservoirs for spreading the virus and as the mediators of some of the major clinical syndromes associated with advanced HIV disease. There has been considerable speculation that they play a pivotal role in the pathogenesis of AIDS, although relatively little is understood regarding their role in the development of AIDS-associated opportunistic infections. In the unique environment of the lung, where alveolar macrophages represent the principal mediators of the host cell immune response against lung pathogens, the influence of HIV infected cells upon pulmonary defense systems is particularly pertinent. The overall objective of this research program is to delineate the mechanisms by which HIV infection of alveolar macrophages contributes to the pulmonary dysfunction that ultimately results in opportunistic infections. These mechanisms encompass both the effects of HIV upon the functioning of the alveolar macrophage, and interactions between HIV and other pathogens found in the immunocompromised lung. With regard to the alveolar macrophage itself, this project is specifically oriented towards understanding the dysregulation of cytokine production in alveolar macrophages resulting from HIV infection and its pathophysiological consequences. Within this project, we will also address the role of CMV, the other virus most commonly associated with AIDS in impairing lung defense mechanisms. Aspects of alveolar macrophage function with respect to infection by P. carinii and mycobacteria will be also investigated within the context of collaborative projects in the program. Our aim is to develop data on the operative dynamics within the pulmonary system of HIV infected individuals, both between different invading organisms and between those organisms and the host tissue, in sufficient molecular detail to then pursue specific strategies designed to interfere with these destructive processes. One specific strategy for intervention is presented which utilizes gene therapy as an outgrowth of the reagents and knowledge base generated in this project.