Fig 4. β-catenin pathway inhibition enhances HIV latency reversal of other drugs.
(A) Treatment of J-Lat 8.4 cells with established LRAs alone (black) or in combination with 100 nM β-catenin inhibitor ADV (red) for 48 hours. Fold change in HIV gag RNA transcript levels over vehicle control (DMSO) is shown. (B) Fold change in HIV gag RNA levels for LRAs used in combination with ADV, normalized to HIV RNA levels when treated with the LRA alone. (C) Percent of cells positive for intracellular HIV GFP reporter after treatment with LRAs alone (black) or in combination with ADV (red). (D) Fold increase in cells positive for HIV protein (GFP) with ADV treatment, normalized to single LRA treatment. Columns indicate mean of 6 replicates with SEM error bars for (a-d). (E) Latent infection of HIV NL4-3 (closed circles) and REJO (open circles) was modeled in primary CD4+ TCM cells from three to four donors and reactivated with αCD3/αCD28 beads and 1 μM prostatin alone (black) or in combination with 100 nM ADV (red) for 48 hrs. Percent reactivation (percent CD4- p24+ cells) is plotted for each donor with connecting lines. (F) Fold change in the percent of CD4 negative HIV p24 positive cells with combination ADV treatment, normalized to single treatment, is shown. Significance was determined using paired t-tests for all panels, * p<0.05, ** p<0.01.