Fig. 1: Gene-expression profiling of virus-specific CD8+ T cells in HCV infection.
From: Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection

a Principal-component analysis (PCA) of 4766 differentially expressed genes (DEGs) identified by ANOVA (q-value ≤ 0.05) in HCV-specific CD8+ T cells from patients with acute (n = 13), chronic (n = 7) and resolved (n = 4) HCV infections, as well as FLU-specific CD8+ T cells from healthy controls (n = 5). Data were normalized with the quantile method and filtered for probes detected in at least two-third of replicates for each condition. b Hierarchical-clustering representation of the 4766 DEGs. Data were median-normalized before clustering and expressed as single patient profiling. In red upregulated and in blue downregulated genes. c Transcriptome profiles of HCV-specific CD8+ T cells from chronically evolving and self-limited acute patients were compared by topological analysis at two different time-points (time of diagnosis/T1 and several months later/T2). Twenty-nine and 277 pathways were significantly dysregulated (Benjamini-Hochberg corrected q-value ≤ 0.05) at the T1/early and T2/late time-points, respectively. Venn-diagram distribution of pathways identified as dysregulated by comparative topological analysis of acute chronically-evolving vs. self-limited and chronic vs. resolved patients. The 15 pathways found to be significantly dysregulated in both comparisons, but with a largely predominant trend toward upregulation (red) at T1/early and the opposite trend (blue) at T2/late, are listed in the bottom panel; these include genes related to TCR signaling, DNA damage response and metabolism at the T1 comparison (each column shows the enrichment in upregulated or downregulated genes in each pathway derived from the calculation of the median gene expression fold change in the comparison of chronically evolving vs. self-limited–T1/early–and of late chronic vs. spontaneously resolved patients–T2/late). d List of the 14 T1/early-specific dysregulated pathways, half of which are upregulated (red), while the remaining half is downregulated (blue). e Heat-map of differentially expressed genes derived from GSEA (Molecular Signature Database, C2 canonical pathways and C5 gene ontology sets) at T1/early time-point, related to cell cycle, DNA damage/DNA repair, cell signaling, mitochondrion and metabolism. Upregulated genes in red; downregulated genes in blue.