Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities

Abstract

HIV enters tissues early after infection, leading to establishment and persistence of HIV reservoirs despite antiretroviral therapy (ART). Viral reservoirs are a major obstacle to the eradication and cure of HIV. CD14 + CD16 + (mature) monocytes may contribute to establishment and reseeding of reservoirs. A subset of monocytes, consisting mainly of CD14 + CD16 + cells, harbors HIV (HIV + ), while the rest remain uninfected, exposed cells (HIV exp ). It is important to identify cells harboring virus to eliminate reservoirs. Using an innovative single-cell RNA sequencing (scRNAseq) pipeline to detect HIV and host transcripts simultaneously, we characterized HIV + and HIV exp primary human mature monocytes with and without ART. HIV + mature monocytes are not a unique subpopulation but rather can be distinguished from HIV exp by differential gene expression. We characterized mature monocyte subpopulations differently impacted by HIV and ART, highlighting their potential contributions to HIV-associated comorbidities. Our data propose therapeutic targets to block HIV + monocyte entry into tissues, preventing establishment and replenishment of reservoirs even with ART.