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.

Ribonucleoprotein complex biogenesis and RNA processing. Gene sets related to ribonucleoprotein complex biogenesis were the most overrepresented annotations among DE genes at 24 hpi (Fig. 2B) . Ribonucleoproteins contribute to diverse functions within the cell, including microRNA synthesis, ribosomal assembly, and translation (12) . This overlap was reflected at the gene level as well. In particular, ribonucleoprotein complex biogenesis shared many DE genes at 24 hpi with another top annotation cluster, RNA processing. This set of genes encoding the ribonucleoprotein component of the RNA processing machinery was almost entirely downregulated and included many members of the heterogeneous nuclear ribonucleoprotein (hnRNP) and small nuclear ribonucleoprotein (snRNP) families. In a network identifying interactions among the proteins encoded by these genes, a number were found to be highly connected (Fig. 3B ). One of these was HNRNPA1 whose gene product regulates the splicing of eukaryotic and viral mRNA (13) . HNRNPA1 and other hnRNP gene products are known to affect the localization of HIV-1 Gag/Pol mRNA, and their overexpression has previously been shown to reduce HIV-1 replication (Fig. 3B) (14) . Other DE genes at 24 hpi related to ribonucleoprotein biogenesis and RNA processing are also known to affect HIV-1 replication directly; these genes include TARDBP (TAR DNA-binding protein 43) whose protein binds the transactivation response (TAR) element of integrated HIV-1 DNA and represses HIV-1 transcription (15) (16) (17) . Downregulation of HNRNPA1, TARDBP, and other related genes may therefore allow more efficient HIV-1 replication in SUP-T1 cells.