Effects of progesterone on the content of CCR5 and CXCR4 coreceptors in PBMCs of seropositive and exposed but uninfected Mexican women to HIV-1

CCR5 and CXCR4 play an important role in the establishment of HIV infection and disease progression. Caucasian people exposed to HIV but uninfected (EU) present a deletion of 32 bp in CCR5 that has not been reported in EU Hispanics from Latin America. Therefore, other factors besides mutations should be involved in this phenomenon. Studies in healthy women have shown that sex hormones such as progesterone (P) can modulate CCR5/CXCR4 expression through an unknown mechanism. The aim of this paper was to determine the role of P in the regulation of CCR5 and CXCR4 in peripheral blood mononuclear cells (PBMCs) of HIV-1 infected and EU women. We analyzed HIV-1-infected women with stable highly active antiretroviral therapy (HAART) with CD4+ cell counts <400/mm3 or diminution of 20%, EU and HIV-1 seronegative healthy controls. 5 × 106 PBMCs, from HIV-1 infected women, EU women and HIV-1 seronegative healthy controls were cultured and incubated with P (10 or 100 nM), RU486 (P antagonist, 1 μM) or P (100 nM) + RU486 (1 μM). CCR5/CXCR4 content was determined by Western blot. Densitometry data were analyzed using Mann–Whitney test. We found that CCR5 content was reduced by P in all groups. In contrast, CXCR4 content was increased by P in healthy controls and in HIV-1 infected women. Interestingly, CXCR4 content was reduced by P in EU. RU486 did not block P effects in any group. These findings suggest that P should participate in the acquisition and progression of HIV-1 infection by modulating CCR5 and CXCR4 expression. P could contribute to the resistance acquisition of HIV by EU through the down-regulation of both coreceptors.

► P regulates HIV coreceptors in PBMCs from HIV seronegative and seropositive women.
► CCR5 expression is down-regulated while that of CXCR4 is up-regulated by P.
► In exposed but uninfected women to HIV, CCR5 and CXCR4 are down-regulated by P.
► P receptor isoforms (PR-A and PR-B) are expressed in PBMCs from women.
► RU486 does not block P effects on CCR5 and CXCR4 expression.