Caveolin-1 and negative modulation of HIV-1 replication

点击翻译按钮获取中文摘要

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.