An HIV-encoded antisense long non-coding RNA epigenetically regulates viral transcription

The abundance of long non-coding RNAs (lncRNAs) and their wide range of functional roles in human cells are fast becoming realized. Importantly, lncRNAs have been identified as epigenetic modulators and consequently play a pivotal role in the regulation of gene expression. A human immunodeficiency virus (HIV) encoded antisense RNA transcript has recently been reported and we sought to characterize this RNA and determine its potential role in viral transcription regulation. The intrinsic properties of this HIV-expressed lncRNA were characterized and the data presented here suggest that it functions as an epigenetic brake to modulate viral transcription. Suppression of this long antisense transcript with small single stranded antisense RNAs resulted in the activation of viral gene expression. This lncRNA was found to localize to the 5'LTR and to usurp components of endogenous cellular pathways that are involved in lncRNA directed epigenetic gene silencing. Collectively, we find that this viral expressed antisense lncRNA is involved in modulating HIV gene expression and that this regulatory effect is due to an alteration in the epigenetic landscape at the viral promoter.