title: Caveolin 1 inhibits HIV replication by transcriptional repression mediated through NF-κB.
abstract: Caveolin 1 (Cav-1), the scaffold protein of a specific membrane lipid raft called caveolae, has been reported to suppress HIV-1 replication. However, the mechanism by which Cav-1 inhibits HIV replication remains unclear. In this study, we investigated the mechanism by which Cav-1 inhibits HIV replication at the level of gene expression. Our results show that Cav-1 represses viral gene expression and that this suppression involves the NF-κB pathway. We used several approaches in different cell types, including primary CD4(+) T cells and macrophages, to demonstrate the role of nuclear factor κB (NF-κB) in Cav-1-mediated inhibition of viral expression. A mutational analysis of the cis-acting element shows that the two NF-κB sites in the U3 region of the long terminal repeat (LTR) are critical for Cav-1-mediated inhibition of viral expression. In the presence of Cav-1, phosphorylation of IKKβ, IKKα, IκBα, and NF-κB p65 is dramatically reduced, while viral gene expression is suppressed. In addition, translocation of NF-κB p65 to the nucleus decreases substantially in the presence of Cav-1. Furthermore, significant inhibition of NF-κB activation and binding to target DNA are evident in the presence of Cav-1. These results establish evidence that Cav-1 inhibits HIV replication by transcriptional repression of viral gene expression and contributes to HIV's persistent infection of macrophages.
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Xiao Mei
authors.initials: XM
authors.lastname: Wang
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nadeau
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lin
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Abbott
authors.forename: Ayalew
authors.initials: A
authors.lastname: Mergia
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D051242:Caveolin 1 / Q000276:immunology*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology; D016328:NF-kappa B / Q000276:immunology*; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000096:biosynthesis*; D014779:Virus Replication
chemical_list: D051242:Caveolin 1; D016328:NF-kappa B; D014764:Viral Proteins