Current insight into HIV-1 persistence from single-cell transcriptome profiling in acutely treated cohorts of infection.

Purpose of review: Antiretroviral therapy is effective in controlling viral load, but there is immediate rebound of virus when treatment is interrupted. This is due to a reservoir of cells harboring HIV which evades immune surveillance and persists in the host. In this review we discuss research leveraging single-cell transcriptomics to examine single-cells from people living with HIV in vivo that can provide insight into these reservoir cells.

Recent findings: Advancements in the field of multiomics, specifically single-cell RNA-sequencing (scRNA-seq), have enabled the profiling of hundreds of thousands of single cells and characterized the heterogeneity of cells in people with HIV. Studies in cohorts of people treated during acute HIV-1 infection have revealed longitudinal changes in immune responses during early infection, discovered novel restriction and latency factors, and identified markers of the cells with virus and the reservoir size.

Summary: Single-cell transcriptomics is a powerful technology that screens the entire transcriptome of an individual cell. When used strategically to investigate samples from cohorts of acute HIV-1 infection, this unbiased omics tool can shed light on the elusive HIV-1 reservoir and unlock strategies for cure.