Integrated single-cell multiomic analysis of HIV latency reversal reveals novel regulators of viral reactivation

Despite the success of antiretroviral therapy, HIV cannot be cured because of a reservoir of latently infected cells that evades therapy. To understand the mechanisms of HIV latency, we employed an integrated single-cell RNA-seq/ATAC-seq approach to simultaneously profile the transcriptomic and epigenomic characteristics of ~125,000 latently infected primary CD4 cells after reactivation using three different latency-reversing agents. Latent CD4D6 cells were treated with HIV latency reversal agents (SAHA/VOR, prostratin, and iBET151) and control (DMSO) for 24 hours and processed for scRNA-seq and scATAC-seq by the 10X Genomics Multiome ATAC + Gene Expression protocol.