Evidence map›Paper›PMID 35429693›Full record

ArticleEBioMedicine2022

Novel role of UHRF1 in the epigenetic repression of the latent HIV-1.

Roxane Verdikt, Maryam Bendoumou, Sophie Bouchat, Lorena Nestola, Alexander O Pasternak, Gilles Darcis, Véronique Avettand-Fenoel, Caroline Vanhulle, Amina Aït-Ammar, Marion Santangelo and 17 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.5field-weighted citation impact, top 15% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 25 citations in OpenAlex.

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  14. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 6 institutions in 3 countries.

Roxane VerdiktService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Maryam BendoumouService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Sophie BouchatService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Lorena NestolaService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Alexander O PasternakDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Amsterdam 1105 AZ, the Netherland.
Gilles DarcisInfectious Diseases Department, Liège University Hospital, Liège 4000, Belgium.
Véronique Avettand-FenoelAP-HP, Hôpital Necker-Enfants-Malades, Service de Microbiologie clinique, Paris 75015, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75006, France; INSERM, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR8104, Paris 75014, France.
Caroline VanhulleService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Amina Aït-AmmarService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Marion SantangeloService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Estelle PlantService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Valentin Le DouceCentre for Research in Infectious Diseases, University College Dublin, Dublin 4, Ireland.
Nadège DelacourtService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Aurelija CicilionytėDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Amsterdam 1105 AZ, the Netherland.
Coca NecsoiService des Maladies Infectieuses, CHU St-Pierre, Université Libre de Bruxelles (ULB), Brussels 1000, Belgium.
Francis CorazzaLaboratory of Immunology, IRISLab, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels 1020, Belgium.
Caroline Pereira Bittencourt PassaesDépartements de Virologie et Immunologie, Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris 75015, France.
Christian SchwartzLaboratoire DHPI EA7292, Université de Strasbourg, Schiltigheim, 67300, France; IUT Louis Pasteur, Université de Strasbourg, Schiltigheim, 67300, France.
Martin BizetLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
François FuksLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
Asier Sáez-CiriónDépartements de Virologie et Immunologie, Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris 75015, France.
Christine RouziouxAP-HP, Hôpital Necker-Enfants-Malades, Service de Microbiologie clinique, Paris 75015, France.
Stéphane De WitService des Maladies Infectieuses, CHU St-Pierre, Université Libre de Bruxelles (ULB), Brussels 1000, Belgium.
Ben BerkhoutDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Amsterdam 1105 AZ, the Netherland.
Virginie GautierCentre for Research in Infectious Diseases, University College Dublin, Dublin 4, Ireland.
Olivier RohrLaboratoire DHPI EA7292, Université de Strasbourg, Schiltigheim, 67300, France; IUT Louis Pasteur, Université de Strasbourg, Schiltigheim, 67300, France.
Carine Van LintService of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium. Electronic address: Carine.Vanlint@ulb.be.
Université Libre de Bruxelles · BEInstitut Pasteur · FRUniversité de Strasbourg · FRUniversity College Dublin · IEDélégation Paris 5 · FRHôpital Necker-Enfants Malades · FR

Funding

ERASE HIV: Enterprise for Research and Advancements to Stop and Eradicate HIVUM1AI164562 · NIAID · EMORY UNIVERSITY · PI Deanna A Kulpa, Mirko Paiardini · 2021 to 2026
$30.0M
NIAID NIH HHS UM1 AI164562
6 · The paper itself

Abstract

backgroundThe multiplicity, heterogeneity, and dynamic nature of human immunodeficiency virus type-1 (HIV-1) latency mechanisms are reflected in the current lack of functional cure for HIV-1. Accordingly, all classes of latency-reversing agents (LRAs) have been reported to present variable ex vivo potencies. Here, we investigated the molecular mechanisms underlying the potency variability of one LRA: the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC).

methodsWe employed epigenetic interrogation methods (electrophoretic mobility shift assays, chromatin immunoprecipitation, Infinium array) in complementary HIV-1 infection models (latently-infected T-cell line models, primary CD4

findingsWe uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) to the HIV-1 promoter. We showed that UHRF1 redundantly binds to the HIV-1 promoter with different binding modalities where DNA methylation was either non-essential, essential or enhancing UHRF1 binding. We further demonstrated the role of UHRF1 in the epigenetic repression of the latent viral promoter by a concerted control of DNA and histone methylations.

interpretationA better understanding of the molecular mechanisms of HIV-1 latency allows for the development of innovative antiviral strategies. As a proof-of-concept, we showed that pharmacological inhibition of UHRF1 in ex vivo HIV

fundingFunding was provided by the Belgian National Fund for Scientific Research (F.R.S.-FNRS, Belgium), the « Fondation Roi Baudouin », the NEAT (European AIDS Treatment Network) program, the Internationale Brachet Stiftung, ViiV Healthcare, the Télévie, the Walloon Region (« Fonds de Maturation »), « Les Amis des Instituts Pasteur à Bruxelles, asbl », the University of Brussels (Action de Recherche Concertée ULB grant), the Marie Skodowska Curie COFUND action, the European Union's Horizon 2020 research and innovation program under grant agreement No 691119-EU4HIVCURE-H2020-MSCA-RISE-2015, the French Agency for Research on AIDS and Viral Hepatitis (ANRS), the Sidaction and the "Alsace contre le Cancer" Foundation. This work is supported by 1UM1AI164562-01, co-funded by National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases.

Indexed as

CCAAT-Enhancer-Binding ProteinsEpigenetic RepressionHIV-1HIV InfectionsUbiquitin-Protein LigasesVirus LatencyAcquired Immunodeficiency SyndromeDecitabineDNA MethylationHumansCCAAT-Enhancer-Binding ProteinsDecitabineUbiquitin-Protein LigasesUHRF1 protein, humanEGCGEpigeneticsHIV-1 latencyReactivationUHRF1

Identifiers

PMID35429693
PMCPMC9038550
OpenAlexW4224030294

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.