EFFECTS OF HIV AND CMV UPON THE ALVEOLAR MACROPHAGE

最近的研究结果清楚地表明，没有真正的“潜伏期” 与艾滋病有关，至少在严格意义上， term.活跃的病毒复制在整个漫长的 临床无症状期，通常在初始 感染这些发现表明病毒本身 在感染者的临床恶化中起着关键作用 单独的.体外和体内数据都证明了 感染和携带HIV病毒。这些细胞 可以作为长寿的移动的水库， 病毒和作为介质的一些主要的临床综合征 与晚期艾滋病有关。取得了相当大 推测他们在发病机制中起着关键作用， 艾滋病，尽管人们对其作用的了解相对较少 与艾滋病相关的机会性感染。 在肺的独特环境中，肺泡巨噬细胞 代表宿主细胞免疫应答的主要介质 对抗肺部病原体，HIV感染细胞对 肺防御系统尤其重要整体 这项研究计划的目的是阐明机制， HIV感染的肺泡巨噬细胞导致 肺功能障碍，最终导致机会性 感染.这些机制包括艾滋病毒对 肺泡巨噬细胞的功能和相互作用 艾滋病毒和其他病原体之间的关系， 肺。关于肺泡巨噬细胞本身，该项目 是专门针对了解失调的 HIV引起的肺泡巨噬细胞中细胞因子的产生 感染及其病理生理后果。在这 项目，我们还将解决CMV的作用，其他病毒最 通常与艾滋病有关，损害肺部防御机制。 肺泡巨噬细胞功能与感染的关系 卡氏肺孢子虫和分枝杆菌也将在 项目中的合作项目。 我们的目标是 开发肺系统内手术动力学数据 艾滋病毒感染者，无论是在不同的入侵 生物体以及这些生物体与宿主组织之间， 足够的分子细节， 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 治疗是试剂和知识库的产物 在这个项目中产生的。

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.