Evidence map›Paper›PMID 35133986›Full record

ArticleThe Journal of clinical investigation2022

The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells.

Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G Mazur, Vennila Mathivanan, Bethany A Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn and 13 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% 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

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 4 countries.

Gabriel DuetteCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Bonnie HienerCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Hannah MorganFaculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Fernando G MazurPost-graduation Program of Evolutionary Genetics and Molecular Biology, Federal University of São Carlos, São Carlos, Brazil.
Vennila MathivananThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Bethany A HorsburghCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Katie FisherCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Orion TongCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Eunok LeeCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Haelee AhnDivision of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
Ansari ShaikThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Rémi FromentinCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Rebecca HohDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Charline Bacchus-SouffanDivision of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
Najla NasrCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Anthony L CunninghamCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Peter W HuntDivision of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
Nicolas ChomontCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Stuart G TurvilleThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Steven G DeeksDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Anthony D KelleherThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Timothy E SchlubFaculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Sarah PalmerCentre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
The University of Sydney · AUUniversity of California, San Francisco · USUNSW Sydney · AUCentre Hospitalier de l’Université de Montréal · CAWestmead Institute for Medical Research · AUUniversidade Federal de São Carlos · BR

Funding

Delaney AIDS Research Enterprise to Cure HIVUM1AI164560 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS, Sharon Ruth Lewin · 2021 to 2026
$32.0M
Viral reservoirs and sanctuaries in HAART - treated patients: role and mechanismsU19AI096109 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SCHACKER, TIMOTHY W · 2011 to 2015
$29.5M
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
Timing of ART and homeostasis of the persistent HIV reservoir in the adultR01AI116368 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUNT, PETER W · 2015 to 2019
$3.7M
Persistent Functional Immune Defects in Treated HIV InfectionK24AI145806 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUNT, PETER W · 2020 to 2024
$921k
NIAID NIH HHS K24 AI145806NIAID NIH HHS R01 AI116368NIAID NIH HHS U19 AI096109NIAID NIH HHS UM1 AI126611NIAID NIH HHS UM1 AI164560
6 · The paper itself

Abstract

Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4+ T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4+ T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4+ T cells when compared with naive, central, and transitional memory CD4+ T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.

Indexed as

HIV-1HIV InfectionsCD4-Positive T-LymphocytesDNA, ViralHumansnef Gene Products, Human Immunodeficiency VirusProvirusesViral LoadDNA, Viralnef Gene Products, Human Immunodeficiency Virusnef protein, Human immunodeficiency virus 1nef protein, Human immunodeficiency virus 2Adaptive immunityAIDS/HIVInfectious diseaseMolecular geneticsT cells

Identifiers

PMID35133986
PMCPMC8970682
OpenAlexW4210905317

What OpenQuestion holds

Textmetadata
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.