title: Progesterone inhibits HIV-1 replication in human trophoblast cells through inhibition of autocrine tumor necrosis factor secretion.
abstract: BACKGROUND
  Progesterone levels are higher in placental barriers during pregnancy, but the effect of progesterone on human immunodeficiency virus type 1 (HIV-1) infection in placental cells has not been addressed. We hypothesize that progesterone may affect HIV infection.
  
  
  METHODS
  Purified trophoblastic cells and trophoblastic cell lines were infected or transfected with HIV-1, and the effect of progesterone was analyzed. Viral replication was measured by viral p24 or viral load quantification. Nuclear factor kappa -B (NF- kappa B) or long terminal repeat (LTR)-dependent transcription was measured by luciferase assays. Expression of chemokine receptors was analyzed by flow cytometry. Tumor necrosis factor (TNF) messenger RNA was assessed by reverse-transcription polymerase chain reaction (RT-PCR) and quantitative RT-PCR.
  
  
  RESULTS
  Progesterone inhibits HIV-1 replication in placental cells at the concentration found in the placental interface, at a postentry step, and does not affect cell surface expression of chemokine receptors. Progesterone did not inhibit basal or induced LTR transcription or NF- kappa B activation. TNF synthesis in placental cells is induced by HIV-1 infection that, in an autocrine manner, activates viral replication, because neutralizing anti-TNF antibodies block it. Progesterone inhibits the induction of TNF synthesis by viral infection and virus or gp-120-induced TNF transcription.
  
  
  CONCLUSIONS
  Our results demonstrate that progesterone inhibits HIV-1 replication in placental cells by reducing TNF levels, which are required for optimal viral replication.
authors.affiliation: Laboratory Inmuno-Biologia Molecular, Hospital General Universitario Gregorio Marañón, Madrid, 28007, Spain.
authors.forename: Laura Diaz
authors.initials: LD
authors.lastname: Muñoz
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Serramía
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000503:physiopathology; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000503:physiopathology; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone