Cell heterogeneity contributes to the variable response of HIV-1 to latency-reversing agents.

Cell heterogeneity influences HIV-1 response to latency-reversing agents by shifting transcriptional variability from promoter-driven to cell state-driven mechanisms.

• Why it matters: Understanding the sources of gene expression variability in HIV-1 latency is crucial for developing effective strategies to target the latent viral reservoir, which remains a major obstacle to curing HIV.
• What they did: The study used a dual-copy MS2-tagging system combined with mathematical analysis to examine HIV-1 transcription variability in live cells, revealing changes in correlation patterns upon stimulation with latency-reversing agents.
• The result: Findings show that cellular heterogeneity shapes the response to these agents and provide mechanistic insights that could inform improved approaches to reactivate latent HIV-1.