Abstract
Spontaneous transcription and translation of HIV can persist during suppressive antiretroviral therapy (ART). The quantity, phenotype, and biological relevance of this spontaneously “active” reservoir remain unclear. Using multiplexed single-cell RNAflow-fluorescence in situ hybridization (FISH), we detect active HIV transcription in 14/18 people with HIV on suppressive ART, with a median of 28/million CD4+ T cells. While these cells predominantly exhibit abortive transcription, p24-expressing cells are evident in 39% of participants. Phenotypically diverse, active reservoirs are enriched in central memory T cells and CCR6- and activation-marker-expressing cells. The magnitude of the active reservoir positively correlates with total HIV-specific CD4+ and CD8+ T cell responses and with multiple HIV-specific T cell clusters identified by unsupervised analysis. These associations are particularly strong with p24-expressing active reservoir cells. Single-cell vDNA sequencing shows that active reservoirs are largely dominated by defective proviruses. Our data suggest that these reservoirs maintain HIV-specific CD4+ and CD8+ T responses during suppressive ART.
Original language | English (US) |
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Pages (from-to) | 1507-1522.e5 |
Journal | Cell Host and Microbe |
Volume | 31 |
Issue number | 9 |
DOIs | |
State | Published - Sep 13 2023 |
Keywords
- HIV
- HIV-specific CD4 T cell responses
- HIV-specific CD8 T cell responses
- antiretroviral therapy
- flow cytometric fluorescence in situ RNA hybridization
- spontaneously active reservoirs
- viral reservoirs
- viral transcription
- viral translation
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Virology