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.

HIV-1 infection does not trigger innate sensing at 12 hpi. Notably, innate immunity was absent from the processes associated with DE genes at 12 hpi, suggesting that HIV-1 infection impaired T cell activation while evading virus-sensing mechanisms ( Fig. 2A) . With the exception of IRF1, which was downregulated at 12 hpi (Fig. 1) , interferon response factors (IRFs) (IRF2, IRF3, IRF7, and IRF9) showed no significant change in expression at 12 hpi (data not shown). Furthermore, specific IRF targets, including IRF3 target genes IFI35, IFI44, ISG15, and ISG20, were also not differentially expressed at this time point (21, 22) . IRF3 targets were of particular interest, as intact cytoplasmic HIV-1 DNA has been shown to activate IRF3 in CD4 Ï© T cells (23) . Our observed lack of IRF3 target gene expression is consistent with previous observations that replicating HIV-1 suppressed IRF3 activity (24) . We also examined the levels of inflammationrelated genes previously observed to be differentially regulated in HIV infection studies (1): ANXA1, B2M, and CD69 (generally upregulated) and CD53, CD71, IL-13, and IL-16 (generally downregulated). These genes were also either not expressed at detectable levels or unchanged in expression at 12 hpi (data not shown).