Fig. 1.

Screen of RNA splicing modulators identifies three potent inhibitors of HIV-1 gene expression. a Structures of compounds tested. b HeLa HIVrtTA∆Mls cells were incubated with 791 (30 µM), 833 (2 µM), or 892 (15 µM) for 24 h in the absence (−) or presence of (+) of Dox and media collected. Effect of compound treatment on HIV-1 virion accumulation in culture supernatant as measured by p24 antigen ELISA and expressed relative to DMSO-treated samples (N ≥ 16, ***p ≤ 0.001). Uninduced, DMSO-treated (DMSO, −Dox) samples were included as negative controls. At left, dose response for 791 (c), 833 (d), or 892 (e) on HIV-1 virion production in culture supernatant was measured by p24 antigen ELISA and expressed relative to p24 Gag levels in DMSO-treated samples (N ≥ 3, *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001). At right, the effect of the compounds on cell metabolism/viability, at the ranges of concentrations tested, was measured using an XTT assay or Trypan blue exclusion as a readout of viable cells and expressed relative to DMSO-treated samples (N ≥ 3, *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001). Error bars indicate standard error of the mean (SEM)