Evidence map›Paper›PMID 39952916›Full record

ArticleNature communications2025

Barcoded HIV-1 reveals viral persistence driven by clonal proliferation and distinct epigenetic patterns.

Tian-Hao Zhang, Yuan Shi, Natalia L Komarova, Dominik Wodarz, Matthew Kostelny, Alexander Gonzales, Izra Abbaali, Hongying Chen, Gabrielle Bresson-Tan, Melanie Dimapasoc and 8 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Tian-Hao Zhang *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4422-5581
Yuan Shi *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA.
Natalia L KomarovaDepartment of Mathematics, University of California San Diego, La Jolla, CA, USA.
Dominik WodarzDepartment of Ecology, Behavior and Evolution, University of California San Diego, La Jolla, CA, USA.
Matthew KostelnyDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.
Alexander GonzalesDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, 90095, USA.
Izra AbbaaliDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, 90095, USA.
Hongying ChenDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.
Gabrielle Bresson-TanDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, 90095, USA.
Melanie DimapasocDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.ORCID http://orcid.org/0000-0003-0328-315X
William HarveyDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, 90095, USA.
Christopher OhDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, 90095, USA.
Camille CarmonaDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.
Christopher SeetDepartment of Medicine, Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, California, USA.ORCID http://orcid.org/0000-0002-4821-1400
Yushen DuCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Ren SunDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA.
Jerome A ZackDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.ORCID http://orcid.org/0000-0001-5486-8495
Jocelyn T KimDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, 90095, USA. jocelynkim@mednet.ucla.edu.ORCID http://orcid.org/0000-0001-7040-5773

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
CRISPR for CureUM1AI164568 · NIAID · TEMPLE UNIV OF THE COMMONWEALTH · PI Tricia Helen Burdo, Kamel Khalili · 2021 to 2026
$27.7M
UCLA-CDU CFARP30AI152501 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Warren Scott Comulada, LaShonda Spencer · 2022 to 2026
$15.6M
Natural killer cell engineering to target the HIV reservoirR01AI161803 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLISH, CATHERINE A, ZACK, JEROME A. · 2021 to 2025
$3.8M
The Effect of Natural Killer Cell-Based Therapy on the HIV ReservoirK08AI155232 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KIM, JOCELYN T · 2020 to 2024
$1.0M
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) AI155232National Science Foundation (NSF) 2152155NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042NIAID NIH HHS K08 AI155232NIAID NIH HHS P30 AI152501NIAID NIH HHS R01 AI161803NIAID NIH HHS UM1 AI164568U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) UL1TR001881U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI127410U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI164568
6 · The paper itself

Abstract

The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring HIV cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays of latently infected cells. This study utilizes barcoded HIV to analyze the reservoir in humanized mice. Using bulk PCR and deep sequencing methodologies, we retrieve 890 viral RNA barcodes and 504 proviral barcodes linked to 15,305 integration sites at the single RNA or DNA molecule in vivo. We track viral genetic diversity throughout early infection, ART, and rebound. The proviral reservoir retains genetic diversity despite cellular clonal proliferation and viral seeding by rebounding virus. Non-proliferated cell clones are likely the result of elimination of proviruses associated with transcriptional activation and viremia. Elimination of proviruses associated with viremia is less prominent among proliferated cell clones. Proliferated, but not massively expanded, cell clones contribute to proviral expansion and viremia, suggesting they fuel viral persistence. This approach enables comprehensive assessment of viral levels, lineages, integration sites, clonal proliferation and proviral epigenetic patterns in vivo. These findings highlight complex reservoir dynamics and the role of proliferated cell clones in viral persistence.

Indexed as

Epigenesis, GeneticHIV-1HIV InfectionsAnimalsCell ProliferationGenetic VariationHumansMiceProvirusesRNA, ViralViral LoadViremiaVirus LatencyRNA, Viral

Identifiers

PMID39952916
PMCPMC11829055

What OpenQuestion holds

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Registered trials

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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.