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Updated: Jun 23, 2026

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Antigen Stimulation Reactivates HIV-1 Proviruses Despite Integration in Repressive Chromatin
Angelica Camilo-Contreras1, Filippo Dragoni1, Hao Zhang2
1Johns Hopkins University, Department of Medicine, Division of Infectious Diseases, Baltimore, MD, USA.
Abstract:
Intact HIV-1 proviruses become progressively enriched in transcriptionally repressive genomic regions during long-term antiretroviral therapy (ART) and in elite controllers, raising questions about their capacity for reactivation in vivo. We used an antigen-restricted quantitative viral outgrowth assay (ag qVOA) to test whether cognate antigen stimulation can reverse latency of proviruses integrated within repressive chromatin. Using cells from two people with HIV (PWH) on ART, one on long-term treatment and one an elite controller, we show that antigen-specific stimulation induces viral outgrowth from intact proviruses integrated into a pericentromeric transition region and a zinc finger gene, respectively. These findings demonstrate that antigen recognition can overcome epigenetic constraints to reactivate proviruses with low inducibility and suggest that proviruses in so-called "deeper latency" may contribute to residual viremia and viral rebound following treatment interruption.
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