EFFECTS OF HIV AND CMV UPON THE ALVEOLAR MACROPHAGE

HIV 和 CMV 对肺泡巨噬细胞的影响

• 批准号: 6110032
• 负责人: JEROME E GROOPMAN
• 金额: $ 29.05万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110032
• 关键词: HIV envelope protein gp120; HIV infections; adeno associated virus group; alveolar macrophages; cellular immunity; colony stimulating factor; cytokine; cytomegalovirus; diagnostic respiratory lavage; endotoxins; enzyme linked immunosorbent assay; gene therapy; host organism interaction; immunomodulators; interleukin 1; interleukin 6; microorganism immunology; nonhuman therapy evaluation; opportunistic infections; polymerase chain reaction; transfection; tumor necrosis factor alpha; virus protein

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.

最近的研究表明，没有真正的“潜伏期”