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.

Innate immunity and the inflammatory response continued to be absent from the significantly upregulated gene sets at 24 hpi (by GSEA [see Fig. S6A in the supplemental material]). IRF1 was more strongly downregulated at 24 hpi than at 12 hpi, but other IRF genes (IRF2, IRF3, IRF7, and IRF9) continued to show no significant change in expression ( Fig. 1 ; data not shown). In a separate experiment, we confirmed that IRF1 was downregulated at 24 hpi by qPCR (by an average of 44%; data not shown). Other interferon (IFN)-inducible genes were differentially expressed at this time point but in different directions, such as B2M and IFI16 (both downregulated) and IFI30 and ISG20 (both upregulated). This lack of concerted change may have offset the detection of interferon response gene sets as up-or downregulated at 24 hpi by GSEA. Instead, at 24 hpi, the related gene sets of cellular defense and immune response were found to be primarily downregulated (by GSEA [Fig. S6B] ). Several of the downregulated genes associated with these gene sets were also associated with T cell activation; these genes include CD1D, CD2, CD28, RAG1, and TNFRSF4 (Fig. S6D) . Additional immune response-specific genes downregulated at 24 hpi included IL4 and IL7R, suggesting that HIV-1 may have impaired the ability of infected cells to signal other cells or respond to extracellular cues.