MACROPHAGE TARGETED THERAPY FOR HAD AND HIV DISEASE; PROJECT #2

巨噬细胞靶向治疗艾滋病毒和艾滋病毒；

• 批准号: 8358005
• 负责人: Susan V. Westmoreland
• 金额: $ 6.84万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358005
• 关键词: AIDS neuropathy; Acquired Immunodeficiency Syndrome; Acute; Animals; Blood; CD14 gene; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Central Nervous System Diseases; Development; Disease; FCGR3B gene; Flushing; Funding; Grant; Guanidines; HIV; Infection; Lymphocyte Depletion; Lymphoid; Macaca mulatta; Modeling; National Center for Research Resources; New England; Pathogenesis; Polyamines; Population; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SIV; Source; Target Populations; Testing; Tissues; United States National Institutes of Health; Viral; analog; base; cost; inhibitor/antagonist; killings; macrophage; monocyte; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This Project within the PPG will investigate, using SIV and SHIV infection rhesus macaques, the effect of polyamine synthesis inhibitors (PBI) on pathogenesis AIDS and sequela of neuroAIDS. For this, we initially propose to investigate the polyamine analogues CG-047, synthetic guanidine compound PA-OO1 and CNI-1493 termed PA-OO2 in this application. We hypothesize the PBI will deactivate and/or selectively target populations of CD14 and CD16 monocyte/macrophages some of which are infected. We proposed to use a) a CD8+ lymphocyte depletion model of SIV infection that results in rapid, consistent and severe CNS disease, and b) a SHIV infection model that rapidly depletes CD4+ T lymphocytes resulting in high SIV replication in monocyte/macrophages, to study the effects of PBI delaying and/reversing CNS disease flushing monocyte/macrophage viral reservoirs. We propose three specific aims to test our hypothesis. Studies in aim 1 will determine whether PBI (PA-OO1 andPA-OO2) deactivate and/or kill select CD14 CD16 monocyte populations resulting in clearance of monocyte/macrophage reservoir of SIV during acute infection and the development of AIDS. Studies in aim 2 test the hypothesis that PBI deactivate and/or kill select CD14 CD16 monocyte populations, inhibiting and/or reversing SIVE. Studies in aim 3 test the hypothesis that PBI administered SHIV infected animals depleted of CD4+ T cells with high monocyte/macrophage SIV replication, clears or diminishes viral reservoirs in blood, lymphoid and CNS tissues.

这个子项目是利用这些资源的众多研究子项目之一