ArticlePLoS pathogens2021
Inhibition of the H3K27 demethylase UTX enhances the epigenetic silencing of HIV proviruses and induces HIV-1 DNA hypermethylation but fails to permanently block HIV reactivation.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 32 citations in OpenAlex.
- Epigenetic dysregulation in osteonecrosis of the femoral head: a critical review of DNA methylation, histone modifications, and clinical translation.Journal of orthopaedic surgery and research · 2026Review
- TRA2A negatively regulates HIV-1-induced macrophage pyroptosis by mediating TXNIP expression in an m6A-dependent manner.Cell death discovery · 2026Article
- Review
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation.Translational psychiatry · 2026Review
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Sex-Specific Factors Influencing HIV Infection.Immunological reviews · 2026Review
- Epigenetic mechanisms of retroviral regulation: a comparative review.Epigenetics & chromatin · 2026Review
- Epigenetic regulation of HIV-1 transcription: insights into latency mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- HIV infection reprogrammes CD4+ T cells for quiescence and entry into proviral latency.Nature microbiology · 2025Article
- Regulation of histone H3K27 methylation in inflammation and cancer.Molecular biomedicine · 2025Review
- Tannic acid reactivates HIV-1 latency by mediating CBX4 degradation.Journal of virology · 2025Article
- Article
- Review
- Cocaine-induced DNA-PK relieves RNAP II pausing by promoting TRIM28 phosphorylation.bioRxiv : the preprint server for biology · 2024Article
- KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.Antiviral research · 2024Article
- Structural rearrangements in the nucleus localize latent HIV proviruses to a perinucleolar compartment supportive of reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Enhancing broadly neutralising antibody suppression of HIV by immune modulation and vaccination.Frontiers in immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
One strategy for a functional cure of HIV-1 is "block and lock", which seeks to permanently suppress the rebound of quiescent HIV-1 by epigenetic silencing. For the bivalent promoter in the HIV LTR, both histone 3 lysine 27 tri-methylation (H3K27me3) and DNA methylation are associated with viral suppression, while H3K4 tri-methylation (H3K4me3) is correlated with viral expression. However, H3K27me3 is readily reversed upon activation of T-cells through the T-cell receptor. In an attempt to suppress latent HIV-1 in a stable fashion, we knocked down the expression or inhibited the activity of UTX/KDM6A, the major H3K27 demethylase, and investigated its impact on latent HIV-1 reactivation in T cells. Inhibition of UTX dramatically enhanced H3K27me3 levels at the HIV LTR and was associated with increased DNA methylation. In latently infected cells from patients, GSK-J4, which is a potent dual inhibitor of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A, effectively suppressed the reactivation of latent HIV-1 and also induced DNA methylation at specific sites in the 5'LTR of latent HIV-1 by the enhanced recruitment of DNMT3A to HIV-1. Nonetheless, suppression of HIV-1 through epigenetic silencing required the continued treatment with GSK-J4 and was rapidly reversed after removal of the drug. DNA methylation was also rapidly lost after removal of drug, suggesting active and rapid DNA-demethylation of the HIV LTR. Thus, induction of epigenetic silencing by histone and DNA methylation appears to be insufficient to permanently silence HIV-1 proviral transcription.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.