Fig. 4

SHIV-induced alterations of genes regulating inflammatory pathways in the PFC white matter. Differential gene expression analysis between SHIV infected and unexposed animals. A Number of differentially expressed genes (DEGs) (adjusted p < 0.01) with respect to SHIV infection status identified in the STS, PFC white matter (w), CN, and HP. B Volcano plots displaying Log fold change (FC) and significance (-log p value) of genes expressed in the STS (Left) and PFCw (Right) after SHIV infection. Colors indicate significant thresholds of genes (p value < 0.01 and False discovery rate (FDR) adjusted p value < 0.10 [blue]; p value < 0.01 [red]; non-significant [black]). C Venn diagram indicating the number of overlapping DEGs from SHIV infected versus uninfected comparisons in the PFCw (P), STS (S), CN (C), and HP (H) (Center). GSEA–KEGG pathway analysis of DEGs exclusive to the PFCw (Left, Red), STS (Right, blue), or shared between the PFCw and STS (Right, gray). Plots indicate fold change by GSEA–GP–BP pathway enrichment between SHIV infected and uninfected animals in the PFCw (Left, Red) and STS (Right, Blue). D Gene set enrichment analysis of transcripts related to alpha beta T cell differentiation GO:0046632 from PFCw DEG profiles (Top) and heatmap showing expression levels of corresponding genes in the PFCw (green) and STS (red) of SHIV infected (pink) and uninfected (black) animals (Bottom). E Expression level of DEGs regulating inflammatory processes, immune cell functions, and synaptic functions in the PFCw of SHIV infected (red) and uninfected (gray) animals. F Gating for activated CD4 T-cells (top) and CD8 T cells (bottom) and frequency of PD1 + , PD1⁺CXCR3⁺, PD1⁺CCR6⁺ CD4 T-cells in the CSF of SHIV infected and uninfected animals over the course of infection. G IP-10 levels in CSF and serum expressed as Median Fluorescence Intensity (MFI) run using Legend plex assay in controls and SHIV infected animals (n = 7 animals infected with SHIV.C.CH505 intravaginally and n = 3 intravenously). H Gating for activated T cells isolated from the PFC, frequency of CXCR3 + CD4 and CD8 T cells in controls versus SHIV infected animals. Symbols indicate individual animals. A, B, F–H P values for gene expression data derived from linear mixed effects model. F, H *P < 0.05 by Wilcoxon sign ranked test. G **P < 0.01 by Mann–Whitney test