Evidence map›Paper›PMID 34636876›Full record

ArticleThe Journal of experimental medicine2021

Integration features of intact latent HIV-1 in CD4+ T cell clones contribute to viral persistence.

Amy S Huang, Victor Ramos, Thiago Y Oliveira, Christian Gaebler, Mila Jankovic, Michel C Nussenzweig, Lillian B Cohn

Open access · hybridAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

56 citing papers in PubMed, 77 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Amy S HuangLaboratory of Molecular Immunology, The Rockefeller University, New York, NY.ORCID 0000-0002-5303-2191
Victor RamosLaboratory of Molecular Immunology, The Rockefeller University, New York, NY.ORCID 0000-0001-7353-3420
Thiago Y OliveiraLaboratory of Molecular Immunology, The Rockefeller University, New York, NY.ORCID 0000-0002-2654-0879
Christian GaeblerLaboratory of Molecular Immunology, The Rockefeller University, New York, NY.ORCID 0000-0001-7295-8128
Mila JankovicLaboratory of Molecular Immunology, The Rockefeller University, New York, NY.ORCID 0000-0001-9696-5234
Michel C Nussenzweig *Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.ORCID 0000-0003-0592-8564
Lillian B Cohn *Fred Hutchinson Cancer Research Center, Seattle, WA.ORCID 0000-0002-3485-8692
Rockefeller University · USFred Hutch Cancer Center · USHoward Hughes Medical Institute · US

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2012 to 2018
$204.7M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI AHMED, RAFI · 2012 to 2018
$131.5M
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6M
REACH: Research Enterprise to Advance a Cure for HIVUM1AI164565 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Marina Caskey, R. Brad Jones · 2021 to 2026
$32.9M
Patient and Population Health Outcomes Research SWGP30AI124414 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Vinayaka R. Prasad · 2017 to 2026
$28.3M
Delaney AIDS Research Enterprise to Cure HIVUM1AI126611 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEEKS, STEVEN GRANT, PICKER, LOUIS J. · 2016 to 2020
$27.9M
First-in-human study of two anti-SARS CoV-2 antibodies in health volunteersUM1AI126620 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J, RILEY, JAMES L. · 2016 to 2021
$24.5M
Optimization of Fc effector activity of anti-HIV antibodies to target HIV reservoirR01AI129795 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C, RAVETCH, JEFFREY VICTOR · 2017 to 2021
$4.2M
Bill & Melinda Gates Foundation OPP1092074Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001866NIAID NIH HHS P30 AI124414NIAID NIH HHS R01 AI129795NIAID NIH HHS UM1 AI100645NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI126611NIAID NIH HHS UM1 AI126620NIAID NIH HHS UM1 AI164565NIH HHS 1P30AI124414-01A1NIH HHS UL1 TR001866NIH HHS UM1AI126611NIH HHS UM1AI164565
6 · The paper itself

Abstract

Latent intact HIV-1 proviruses persist in a small subset of long-lived CD4+ T cells that can undergo clonal expansion in vivo. Expanded clones of CD4+ T cells dominate latent reservoirs in individuals on long-term antiretroviral therapy (ART) and represent a major barrier to HIV-1 cure. To determine how integration landscape might contribute to latency, we analyzed integration sites of near full length HIV-1 genomes from individuals on long-term ART, focusing on individuals whose reservoirs are highly clonal. We find that intact proviruses in expanded CD4+ T cell clones are preferentially integrated within Krüppel-associated box (KRAB) domain-containing zinc finger (ZNF) genes. ZNF genes are associated with heterochromatin in memory CD4+ T cells; nevertheless, they are expressed in these cells under steady-state conditions. In contrast to genes carrying unique integrations, ZNF genes carrying clonal intact integrations are down-regulated upon cellular activation. Together, the data suggest selected genomic sites, including ZNF genes, can be especially permissive for maintaining HIV-1 latency during memory CD4+ T cell expansion.

Indexed as

AdultAnti-HIV AgentsCD4-Positive T-LymphocytesFemaleHIV-1HIV InfectionsHost-Pathogen InteractionsHumansKruppel-Like Transcription FactorsMaleMiddle AgedProvirusesVirus IntegrationVirus LatencyAnti-HIV AgentsKruppel-Like Transcription Factors

Identifiers

PMID34636876
PMCPMC8515646
OpenAlexW3207616439

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.