Effect of Progesterone, Cortisol and Dhea on the ITR of maedivisna virus transcripcional activity

Abstract

Previous studies suggest that steroid hormones may direct the expression of Maedi-Visna virus (MVV), as has been observed in other retroviral infections. This would be achieved through the promoter/regulator region of the LTR (long terminal repeats) of the proviral genome, which would contain hormone responsive elements (HRE). The aim of this study was to evaluate the effect of cortisol, progesterone and dehydroepiandrosterone (DHEA) on the transcriptional ability of the MVV LTR region. For this, sheep fibroblasts were transfected with pAcGFP plasmids (containing the gene for green fluorescent protein, GFP) in which the U3-cap region of the LTR of different strains of MVV had been cloned. Different concentrations of each hormone were added to transfected cells and the transcriptional activity of the LTR was evaluated after 48 hours of incubation by quantifying the expression of GFP by flow cytometry. A clear inhibitory effect of the transcriptional ability of the LTR was observed in most of the assays at high hormonal concentrations. This effect decreased with the increasing dilutions of the hormones, to the point that GFP expression was above baseline in cells transfected with several of the plasmids and treated with dilutions above 10-7M of cortisol and DHEA. In general terms, a different response could not be associated to the origin of the strain under study, suggesting that the effect of steroids is not related to the different origins/tropisms of the virus. These data suggest the presence of a hormone responsive element (HRE) in the MVV LTR able to respond to hormonal stimulation.