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.

Suppression of T cell functionality persists and expands at 24 hpi. As was the case at 12 hpi, genes related to T cell activation and differentiation were predominantly downregulated at 24 hpi. All of the T cell activation-related DE genes at 12 hpi continued to exhibit the same direction of change at 24 hpi (Fig. 1 ). Other T cell activation-related genes DE at 24 hpi included CD3D, CD3Q, and RHOH, all of which encode membrane proteins crucial for T cell receptor function. A network depicting known interactions among proteins encoded by T cell activation-related DE genes at 24 hpi showed two highly connected nodes: LCK (lymphocytespecific protein kinase) and TP53 (p53), both of which were strongly downregulated at 24 hpi (Fig. 3A) . Our observed downregulation of TP53 differed from the upregulation observed in previous microarray studies and may indicate a cell type-specific effect (1) . Genes involved in other core T cell functions, such as proliferation, survival, and antigen presentation, were also downregulated at 24 hpi. These genes included CD1D, CD28, CXCR4, TNFRSF4, and TREML2. TOB1 (transducer of ERBB2), a negative regulator of T cell activation, proliferation, and interleukin 2 (IL-2) production, showed increased expression and may contribute to the downregulation observed in other genes (data not shown). A connection between TOB1 expression and HIV-1 infection has not previously been mentioned. Overall, the increased number of DE genes related to T cell activation indicated increased suppression of this pathway by 24 hpi.