Progesterone inhibits HIV-1 replication in human trophoblast cells through inhibition of autocrine tumor necrosis factor secretion.
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.
Muñoz
Laura Diaz
LD
Laboratory Inmuno-Biologia Molecular, Hospital General Universitario Gregorio Marañón, Madrid, 28007, Spain.
Serramía
Maria Jesús
MJ
Fresno
Manuel
M
Muñoz-Fernández
Maria Angeles
MA
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*
D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone