Simmons Glenn E, Taylor Harry E, Hildreth James E K
Department of Microbiology and Immunology, Meharry Medical College, Nashville, TN 37208, USA.
Virology. 2012 Oct 10;432(1):110-9. doi: 10.1016/j.virol.2012.05.016. Epub 2012 Jun 28.
Caveolin-1 is an integral membrane protein primarily responsible for the formation of membrane structures known as caveolae. Caveolae are specialized lipid rafts involved in protein trafficking, cholesterol homeostasis, and a number of signaling functions. It has been demonstrated that caveolin-1 suppresses HIV-1 protein expression. We found that co-transfecting cells with HIV-1 and caveolin-1 constructs, results in a marked decrease in the level of HIV-1 transcription relative to cells transfected with HIV-1 DNA alone. Correspondingly, reduction of endogenous caveolin-1 expression by siRNA-mediated silencing resulted in an enhancement of HIV-1 replication. Further, we observed a loss of caveolin-mediated suppression of HIV-1 transcription in promoter studies with reporters containing mutations in the NF-κB binding site. Our analysis of the posttranslational modification status of the p65 subunit of NF-κB demonstrates hypoacetylation of p65 in the presence of caveolin-1. Since hypoacetylated p65 has been shown to inhibit transcription, we conclude that caveolin-1 inhibits HIV-1 transcription through a NF-κB-dependent mechanism.
小窝蛋白-1是一种整合膜蛋白，主要负责形成被称为小窝的膜结构。小窝是参与蛋白质运输、胆固醇稳态及多种信号功能的特殊脂筏。已证实小窝蛋白-1可抑制HIV-1蛋白表达。我们发现，将HIV-1与小窝蛋白-1构建体共转染细胞，相对于仅用HIV-1 DNA转染的细胞，HIV-1转录水平显著降低。相应地，通过siRNA介导的沉默降低内源性小窝蛋白-1表达会导致HIV-1复制增强。此外，在使用含有NF-κB结合位点突变的报告基因进行的启动子研究中，我们观察到小窝蛋白介导的对HIV-1转录的抑制作用丧失。我们对NF-κB的p65亚基的翻译后修饰状态分析表明，在存在小窝蛋白-1的情况下，p65发生低乙酰化。由于低乙酰化的p65已被证明可抑制转录，我们得出结论，小窝蛋白-1通过NF-κB依赖性机制抑制HIV-1转录。
