%0 Journal Article
%T Retinoic acid and liver X receptor agonist synergistically inhibit HIV infection in CD4+ T cells by up-regulating ABCA1-mediated cholesterol efflux
%A Hong Jiang
%A Yunden Badralmaa
%A Jun Yang
%A Richard Lempicki
%A Allison Hazen
%A Ven Natarajan
%J Lipids in Health and Disease
%D 2012
%I BioMed Central
%R 10.1186/1476-511x-11-69
%X Treatment with ATRA dramatically up-regulated ABCA1 expression in CD4+ T cells in a time and dose dependent manner. The expression of ABCA1 paralleled with increased ABCA1-dependent cholesterol efflux. This induction was dependent on T cell receptor (TCR) signaling and ATRA failed to induce ABCA1 expression in resting T cells. Moreover, ATRA and liver X receptor (LXR) agonist-TO-901317 together had synergistic effect on ABCA1 expression as well as cholesterol efflux. Increased ABCA1 expression was associated with lower cellular cholesterol staining. Cells treated with either ATRA or TO-901317 were less vulnerable to HIV-1 infection. Combination of retinoic acid and TO-901317 further inhibited HIV-1 entry and their inhibitory effects could be reversed by cholesterol replenishment.ABCA1 RNA and protein were determined by real-time PCR and immuno blot methods in cells treated with ATRA. Cholesterol efflux rate was measured in cells treated with ATRA and TO-901317.ATRA up-regulates ABCA1 expression and cholesterol efflux in CD4+ T cells and combination of ATRA and liver X receptor (LXR) agonist further enhanced these effects. Increased cholesterol efflux contributed to reduced HIV-1 entry, suggesting that anti-HIV effect of ATRA is mediated through ABCA1.Lipid components of the cell membrane are important for normal cell function. Cholesterol is one of the most important regulators of lipid organization. It is also the major component of lipid rafts, which are the centers for assembling of signaling molecules and membrane protein trafficking [1]. Lipid rafts are also believed to be sites for HIV-1 entry, assembly and budding [2-5]. Cholesterol on both viral and cellular membrane is required for successful HIV-1 infection. Down-regulation of cholesterol from HIV-1 target cells dramatically inhibited both HIV-1 entry and virus particle production [6,7]. Removal of the cholesterol from HIV-1 with cholesterol extraction reagent ¦Â-cyclodextrin resulted in a dose-dependent in
%K ABCA1
%K ATRA
%K retinoic acid
%K TO-901317
%K RAR
%K RXR
%K LXR
%K cholesterol efflux
%K HIV-1
%K CD4+ T cells
%U http://www.lipidworld.com/content/11/1/69