Science Advances· 2026Q1
Cell heterogeneity contributes to the variable response of HIV-1 to latency-reversing agents
- 1citations
- Q1SCImago
- 2026year
Short summary
HIV-1 proviruses within the same cell show uncorrelated transcription in the basal state, driven by promoter stochasticity, but become correlated upon stimulation with latency-reversing agents, indicating cell state-driven variability and explaining differential drug responses.
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Key points
- HIV-1 proviral transcription is uncorrelated within cells in the basal state, attributed to promoter stochasticity.
- Latency-reversing agents shift HIV-1 transcription variability from promoter-driven to cell state-driven.
- Cellular heterogeneity explains the variable responses observed across cells to latency-reversing agents.
- Quantitative tools can dissect sources of transcriptional noise in HIV-1 latency.
AI-generated from the title and abstract; the full text is not read.
Abstract
Transcriptional noise contributes to gene expression variability, but its origin and impact in HIV-1 latency remain incompletely characterized. Here, we combine a dual-copy MS2-tagging system with dedicated mathematical analysis to investigate the variability of HIV-1 transcription in live cells. In the basal state, the transcriptional activity of proviruses located in the same cell was uncorrelated, indicating that expression variability primarily comes from the intrinsic stochasticity of promoter dynamics. Upon stimulation with diverse latency-reversing agents, transcription of viral copies became more correlated within cells than across them, revealing a shift from promoter-driven to cell state-driven variability. Analysis of the molecular drug targets confirmed variable effects across cells. Our findings indicate that cellular heterogeneity can shape the response to latency-reversing agents and demonstrate how quantitative tools can dissect noise sources. This work offers mechanistic insights into HIV-1 latency and informs strategies to target the latent viral reservoir.
The authors' abstract, as published at the source. Science Advances, 2026 · DOI ↗
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VirologyImmunology and Microbiology