Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line

Chang, Stewart T.; Sova, Pavel; Peng, Xinxia; Weiss, Jeffrey; Law, G. Lynn; Palermo, Robert E.; Katze, Michael G.

We complemented functional analysis in DAVID by gene set enrichment analysis (GSEA). This method does not rely on the prior determination of DE genes (e.g., by applying a P value threshold) but instead uses a ranked gene list as input and is therefore well suited for identifying annotations among genes with small-magnitude changes in expression (11) . GSEA identified additional genes that were downregulated and contributed to the suppression of T cell activation; these genes include the CD2, CD4, CD7, CD28, and SIT1 genes encoding T cell-specific surface molecules (see Fig. S4 in the supplemental material). Many of the genes associated with T cell activation in DAVID and GSEA also had roles in other pathways, indicating possible pleiotropic effects (e.g., ADORA2A and RAG1 which also contribute to caspase activity [ Fig. 1]) .