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.
Bibliographical noteFunding Information:
We thank Dr. Robert Nabi for providing caveolin-1-RFP constructs to this study. Dr. Bindong Liu and the FACS/BSL3 Core service and RCMI grant Award Number G12RR003032 from the National Center for Research Resources for use of facilities. The work described in this study was supported by National Institutes of Health grants F31 AI082950 (G.E.S), T32 AI007281 (G.E.S), and Vanderbilt Institute for Clinical and Translational Research Scholar Award 5 KL2 RR024977-03 (H.E.T.).