Caveolin-1 and negative modulation of HIV-1 replication

Caveolin-1 和 HIV-1 复制的负调节

• 批准号: 7679173
• 负责人: Glenn Edward Simmons
• 金额: $ 3.43万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7679173
• 关键词: AIDS/HIV problem; Address; Adverse effects; Affect; Binding Proteins; Biogenesis; Biology; Caveolae; Caveolins; Cell membrane; Cells; Cessation of life; Cholesterol; Cholesterol Homeostasis; Data; Event; Genes; Genetic Transcription; Goals; HIV; HIV Infections; HIV-1; Infection; Integral Membrane Protein; Integration Host Factors; Life; Link; Mediating; Membrane Microdomains; Methods; Pathway interactions; Peripheral Blood Mononuclear Cell; Plague; Prevention; Prevention strategy; Regulation; Regulatory Element; Role; Signal Transduction; Solutions; Sterols; T-Lymphocyte; Time; Up-Regulation; Work; base; caveolin 1; cholesterol-binding protein; effective therapy; inhibitor/antagonist; insight; macrophage; novel; novel therapeutics; promoter; protein expression; public health relevance; response; success

DESCRIPTION (provided by applicant): Caveolin-1, an integral membrane protein highly localized to lipid rafts, has been shown to cause marked decrease in HIV-1 protein expression. Caveolae, the plasmalemmal invaginations formed by caveolin oligomerization, are involved in regulation of intracellular cholesterol levels. The connections between cholesterol and HIV-1 biology have been well established through studies performed by our lab and others. The work described in this proposal will focus on further defining that link by elucidating the relationship between caveolin-1 and HIV-1 biogenesis. We hypothesize that caveolin-1 negatively affects HIV-1 replication via a cholesterol dependent mechanisms at the transcriptional level. To address this hypothesis, Aim 1 of this study will seek to identify the pathways involved in caveolin-mediated HIV-1 inhibition. Aim 2 will examine the effects of differential expression of caveolin-1 on HIV-1 biogenesis in T cells and macrophages. The long-term goal of this study is to identify novel host factors capable of restricting HIV-1 replication. Thus far, HIV/AIDS has plagued the globe for nearly 30 years and in that time, few breakthroughs have accompanied the ever-increasing death toll. Anti-retrovirals have been an effective treatment, however access and use of them, and the subsequent side effects, is far from an optimal solution. PUBLIC HEALTH RELEVANCE: Prevention methods have had little success to date. Identifying host factors that can suppress HIV expression, like caveolin-1, could provide insight to novel therapeutic or preventive strategies.

描述（由申请人提供）：Caveolin-1是一种高度局部到脂质筏的整体膜蛋白，已显示出可引起HIV-1蛋白表达的明显降低。小窝是由小窝素寡聚形成的浆膜内部衰减，参与了细胞内胆固醇水平的调节。通过我们的实验室和其他人进行的研究，胆固醇与HIV-1生物学之间的联系已经很好地建立。本提案中描述的工作将集中于进一步定义这种联系通过阐明小窝蛋白-1和HIV-1生物发生之间的关系。我们假设Caveolin-1通过转录水平的胆固醇依赖机制对HIV-1复制产生负面影响。为了解决这一假设，本研究的目标1将寻求识别可爱素介导的HIV-1抑制作用所涉及的途径。 AIM 2将检查小窝蛋白-1的差异表达对T细胞和巨噬细胞中HIV-1生物发生的影响。这项研究的长期目标是确定能够限制HIV-1复制的新型宿主因素。到目前为止，艾滋病毒/艾滋病困扰着全球近30年，在那段时间里，很少有突破伴随着越来越多的死亡人数。抗逆转录病毒是一种有效的治疗方法，但是它们的使用和使用，随后的副作用远非最佳解决方案。公共卫生相关性：迄今为止，预防方法几乎没有成功。识别可以抑制诸如小窝蛋白-1之类的艾滋病毒表达的宿主因素可以为新颖的治疗或预防策略提供见解。