Single cell analysis of quiescent HIV infection reveals host transcriptional profiles that regulate proviral latency

The latent HIV reservoir is diverse, but most studies of HIV latency have used bulk cell assays. Here we characterized cell line and primary cell models of HIV latency with single cell qPCR (sc-qPCR) for viral RNA (vRNA), and single cell RNAseq (scRNAseq). sc-qPCR revealed distinct populations of cells transcribing vRNA across a wide range of levels. Strikingly, scRNAseq of latently infected primary cells revealed a relationship between vRNA levels and the transcriptomic profiles within the population. Cells with the greatest level of HIV silencing expressed a specific set of host genes including markers of central memory T cells. By contrast, latently infected cells with higher levels of HIV transcription expressed markers of activated and effector T cells. These data reveal that heterogeneous behaviors of HIV proviruses within the latent reservoir are influenced by the host cell transcriptional program. Therapeutic modulation of these programs may reverse or enforce HIV latency.