Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts
- Philip K. Ehrenberg
- Aviva Geretz
- Meta Volcic
- Taisuke Izumi
- Lauren K. Yum
- Adam Waickman
- Shida Shangguan
- Dominic Paquin-Proulx
- Matthew Creegan
- Meera Bose
- Kawthar Machmach
- Aidan McGraw
- Akshara Narahari
- Jeffrey R. Currier
- Carlo Sacdalan
- Nittaya Phanuphak
- Richard Apps
- Michael Corley
- Lishomwa C. Ndhlovu
- Bonnie Slike
- Shelly J. Krebs
- Jintanat Anonworanich
- Sodsai Tovanabutra
- Merlin L. Robb
- Michael A. Eller
- Gregory M. Laird
- Joshua Cyktor
- Eric S. Daar
- Trevor A. Crowell
- John W. Mellors
- Sandhya Vasan
- Nelson L. Michael
- Frank Kirchhoff
- Rasmi Thomas
2025-05-29
Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.