Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection

Chang, Stewart T.; Thomas, Matthew J.; Sova, Pavel; Green, Richard R.; Palermo, Robert E.; Katze, Michael G.

Transcriptional regulation impacted by altered microRNA expression. We identified a small number of additional pathways and functions that were enriched in the predicted mRNA targets of DE microRNAs. These annotations included "transcription regulator activity," whose associated mRNAs were upregulated at 24 hpi. This dense network of transcriptional regulators includes cofactors that are known to contribute to HIV replication, namely, KAT2B, also known as PCAF (P300/CBP-associated factor) (14) . Our analysis showed that microRNAs of the miR-17-92 cluster-known to be relevant to T cell function (27) -and miR-32 may target KAT2B and other transcription factors coordinately regulated with KAT2B. In particular, miR-32 has not previously been associated with HIV cofactor expression. Our results suggest that HIV-1 infection may suppress several microRNAs with overlapping specificities to effect HIV cofactor expression.