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.

In previous studies where small RNA-Seq has been applied to HIV-infected cells, the focus has typically been on virally encoded microRNAs or on single time points, providing static snapshots of infection (8) (9) (10) (11) . In this article, we report the use of NGS to observe dynamic changes in cellular small RNAs from HIV-infected CD4 Ï© cells. To this end, we sampled multiple time points, including those preceding detectable HIV replication, to identify signatures of different stages of infection in vitro. To characterize mi-croRNAs, both known and putatively novel, we then integrated our NGS data set with mRNA-Seq data derived from the same experimental samples (1) and thereby identified microRNAs that may contribute to phenotypic changes in infected cells over time. We also provide a full account of putatively novel microRNAs and other small RNAs that were DE upon infection that may in turn provide new avenues for future research.