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.

Finally, we compared our results from NGS to other types of data available regarding HIV-infected cells, including proteinprotein interaction (PPI) data and small interfering RNA (siRNA)-based screens. In an analysis of HIV-related PPI data, van Dijk et al. (37) identified sets of human proteins highly connected to host and viral proteins (37) . Several proteins related to T cell activation were identified as highly connected; these proteins included CD4, CXCR4, and LCK (see Table S4 in the supplemental material). Downregulation of these members, as we observed, would therefore potentially affect the functions of many other proteins as well. Together, these data emphasize the high degree to which HIV-1 suppressed this pathway. In addition, many of the pathways associated with DE genes were identified as essential for HIV-1 replication in a recent meta-analysis of siRNA-based screen data (38) . These pathways included DNA binding, RNA splicing, RNA export, nuclear transport, and protein complex assembly (Table S3) . While the siRNA data suggest that HIV-1 ini-tially requires these pathways to be active to establish an infection, our data suggest that HIV-1 also later suppresses and inactivates these pathways during active replication.