Progesterone Inhibits HIV‐1 Replication in Human Trophoblast Cells through Inhibition of Autocrine Tumor Necrosis Factor Secretion
1Laboratory Inmuno‐Biología Molecular, Hospital General Universitario Gregorio Marañón and 2Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain
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 κ‐B (NF‐κB) 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‐κB 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.
Conclusion.Our results demonstrate that progesterone inhibits HIV‐1 replication in placental cells by reducing TNF levels, which are required for optimal viral replication.
Received 9 February 2006; accepted 4 November 2006; electronically published 23 March 2007.
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Potential conflicts of interest: none reported.
Financial support: M.A.M.‐F. received support from Fundación para la Investigación y Prevención del SIDA en España (FIPSE) (grant 36536‐05), Fondos para la Investigación Sanitaria (grant 040883), and Salud y Farmacia (grant 06778); M.F. received support from SAF (grants 0920‐03 and 05109‐04) and Comunidad Autónoma de Madrid (grant 08.3/0023.1/2001); M.A.M.‐F. and M.F. received support from FIPSE (grant 36514‐05) and Red Temática Cooperativa de Investigación en SIDA (grant RIS G03/173); Asociación Españda de Pediatria 2005‐54 Congreso de la Asociación Española de Pediatría, Murcia (poster no. P322).