Estrogen stimulates transcription of human immunodeficiency virus type 1 (HIV-1)

Gene expression from human immunodeficiency virus (HIV) provirus is a crucial step for the viral replication. Here we examined a potential role of 17β-estradiol (E2) in HIV-1 transcription. Transient luciferase expression studies revealed that E2 activated HIV-LTR reporter gene in HEK293 cells when the cells were co-transfected with estrogen receptor α (ERα) but not ERβ expression plasmid. This E2 effect was abrogated by a specific antagonist to ER, ICI 182,780, indicating that it was mediated by ERα. Mutation analysis revealed that Sp1 binding site but not nuclear factor-kappa B (NF-κB) binding site of HIV-1 LTR is critical to the E2 effect. In addition, whereas E2 could not induce DNA-binding activity of NF-κB, E2 could augment both Sp1 DNA-binding and transcriptional activity. These findings suggest a contribution of estrogen for HIV-1 replication through ERα by augmenting Sp1 DNA-binding and transcriptional activity.