Extended Data Fig. 2: Induction of antivirals pre-ATI in combo-treated RMs.
From: TGF-β mediates epigenetic control of innate antiviral responses and SIV reservoir size
A. STAT and IRF3 phosphorylation levels correlated to virological readouts 24 weeks post-ATI. Only features modulated by combo treatment and correlated to all virological readouts are shown. Differences across groups were assessed with t-statistics of linear regression coefficients. The p-value was corrected for multiple comparisons with the Benjamini–Hochberg method and only features with adjusted p-value < 0.05 were selected for downstream steps. Correlations with virological readouts were calculated using a two-sided Spearman method and only features with an FDR-corrected p-value < 0.1 are shown. Arrows at the bottom of the heatmap indicate CA-vDNAlo combo-treated RMs. B. A bar plot was used to illustrate differences in the number of DEGs (LIMMA P < 0.05, Y axis) in LNMCs and PBMCs from RMs treated with aIL-10 alone and combo-treated RMs pre-ATI. Red represents upregulated genes and blue represents downregulated genes in combo-treated RMs versus aIL-10 treated RMs. The Y axis represents the number of DEGs. C. Heatmap illustrating the differential levels of relative expression of LEGs belonging to the IFN and RFs gene sets in LNMCs from RMs treated with aIL-10 alone (red annotation) and combo-treated RMs (blue annotation) pre-ATI (light green annotation). LEGs from IFN pathways were summarized into a SLEA representation (z-score per pathway per sample). Rows represent genes and columns represent individual RMs. A gradient was used to depict relative levels of gene expression, where blue represents low relative expression and red represents high relative expression. The levels of CA-vRNA, CA-vDNA and 2-LTR circles (white to blue, green and purple, respectively) are annotated at the top of the heatmap. Note the higher levels of expression of antiviral genes in a subgroup of combo-treated RMs with low CA-vDNA (boxed). n = 20 RMs. 2-LTRs: 2-long terminal repeats circles; ATI: analytical treatment interruption; CA-vDNA: cell-associated viral DNA; CA-vRNA: cell-associated viral RNA; DEGs: differentially expressed genes; IFN: interferon; LEGs: leading-edge genes; LIMMA: linear models for microarray and RNA-Seq data; LNMCs: lymph node mononuclear cells; PBMCs: peripheral blood mononuclear cells; RMs: rhesus macaques.
