Regulation of transcriptomic profile by ZL0580 and JQ1
Epigenetic suppression and durable silencing of HIV represent a promising strategy to achieve ART-free remission, consistent with the “block and lock” HIV cure paradigm. BRD4 is a host epigenetic reader and plays a critical role in HIV transcriptional regulation. We previously identified ZL0580, a first-in-class BRD4-selective small molecule that epigenetically suppresses HIV, whereas the pan-BET/BRD4 inhibitor JQ1 activates HIV transcription. The present study utilizes RNA-Sequencing (RNA-Seq) to examine the impact of ZL0580 and JQ1 on transcriptomic profile in the latently HIV-infected J-Lat cells (Clone 10.6). In summary, ZL0580 induces a transcriptomic profile opposing to that induced by JQ1, which is highly consistent the opposing effects of the two compounds on HIV transcription and latency. Overall design: J-Lat cells (10.6) were treated with DMSO (as negative control), ZL0580 (5 uM), or JQ1 (5 uM). 24 hours after treatment, cells were subjected to bulk RNA-Seq analysis.