Identify potential regulators in HIV-1 latency by joint microRNA and mRNA analysis

Abstract

Background/Aims: The main obstacle to cure HIV infection is the existence of long-lasting latent reservoirs. Many efforts have been made to understand basal mechanisms of HIV-1 latency, in which miRNAs play an important role. However, integrated analysis of miRNA and mRNA expression in HIV-1 latency is lacking. Methods and Results: Global miRNA and mRNA expression was determined by microarrays and quantitative reverse transcription PCR in well-characterized HIV-1 latently and actively infected cells, respectively. Interactions of miRNA-mRNA, mRNA-mRNA, and transcription factor-miRNA pairs were assembled into the function network. Our results show that transcription regulation related genes were mostly enriched in HIV-1 latently infected cells. Gene set enrichment analysis revealed nuclear transport related pathways were up-regulated in the latency group. Network dynamic analysis highlighted many gene-pairs sharing the largest changes in different HIV-1 infection state. 83.33% miRNA-target pairs were validated against database, and RHOB related genes constitute the interface between HIV-1 latency and replication state. Conclusion: We show for the first time a joint miRNA and mRNA expression profile related to a HIV-1 latency phenotype, outline a dynamic network of potential regulators involving in HIV-1 latency or replication state, and gain new insights into the source messages for affecting HIV-1 latency.