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.

Early regulation of host transcription factors. We also observed discordance between the large amount of viral RNA present (~20% of total mappable RNA) and the limited amount of altered host gene expression at 12 hpi (~1% of detectable gene loci). That is, despite the use of host machinery and the presence of foreign mRNA, host transcription remained relatively unchanged. This result suggests that at 12 hpi, viral transcription occurred on top of largely undisturbed transcription of host genes. The host genes that we detected as differentially expressed at 12 hpi showed that T cell activation and differentiation were suppressed in in- fected cells, likely via the downregulation of T cell activationspecific transcription factors (BCL11B, IRF1, IKZF1, and SOX4) . The regulation of these and transcription factors specific for other functions (e.g., EGR1, KLF13, and MYC) may explain how HIV initiated replication with minimal disruption to host gene expression at 12 hpi but elicited larger-scale changes later in infection.