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.

Limited upregulation of host processes at 24 hpi. Despite the presence of an almost equal number of up-and downregulated genes at 24 hpi, relatively few gene sets (functions, processes, or pathways) were associated with upregulated genes. When up-and downregulated DE genes at 24 hpi were analyzed separately, more annotation clusters were observed among downregulated genes (70 versus 13 among upregulated genes with significance defined by modified Fisher's exact test as P Ͻ 0.05). A similar result was obtained by GSEA (see Fig. S6A and S6B in the supplemental material). These results suggested that upregulated genes were distributed across many gene sets with few occurring in particular functions or pathways. Among the few upregulated pathways were stress-activated/Jnk cascade signaling and ion transport (Fig. S6C) . Consistent with these observations, HIV-1 Nef has been shown to activate Jnk signaling, ultimately activating the caspase cascade and triggering cell death (20) . The triggering of apoptosis at 24 hpi is consistent with our observation that infected cells began to die following the 24-hpi time point.