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.

Large-scale disruptions to host transcription near peak viral replication. By 24 hpi, extensive reprogramming of the host transcriptome affecting a multitude of pathways had occurred. Remarkably, these large-scale changes occurred without concerted upregulation of innate immunity at the gene set level, suggesting that HIV-1 evaded viral sensing mechanisms. By this time point, the most affected pathways related to RNA fate determination, including RNA processing. While HIV-related RNA processing has been studied intensively, the contribution of most host factors remains incompletely defined (32) . Modulation of this pathway by the virus may allow the proportion of unspliced, partially spliced, and fully spliced HIV RNA to be adjusted depending on the stage of the HIV life cycle. Our finding that over 150 genes related to RNA processing were differentially expressed suggests that HIV-1 infection results in a more complete modulation of RNA processing than previously identified (5, 33) . However, our observed downregulation of RNA processing was consistent with results from an earlier study using NGS to investigate changes in CD4 Ï© T lymphoblasts infected with an HIV-based, nonreplication-competent vector at 24 hpi (34) . Altered regulation of this and other pathways has been observed using microarrays as well, although in general, we observed changes in greater numbers of genes affecting these pathways using NGS (3, 5, 33, 35, 36) .