Evidence map›Paper›PMID 27644592›Full record

ArticleeLife2016

Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells.

Erik C Hansen, Monica Ransom, Jay R Hesselberth, Nina N Hosmane, Adam A Capoferri, Katherine M Bruner, Ross A Pollack, Hao Zhang, Michael Bradley Drummond, Janet M Siliciano and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
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  10. Review
  11. Development of a NovelJournal of virology · 2021
    Article
  12. Article
  13. Article
  14. Detection of Genomic Uracil Patterns.International journal of molecular sciences · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Article
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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

12 authors at 3 institutions in 1 country.

Erik C HansenDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.
Monica RansomDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States.
Jay R HesselberthDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States.
Nina N HosmaneDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
Adam A CapoferriDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
Katherine M BrunerDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
Ross A PollackDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
Hao ZhangW Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.
Michael Bradley DrummondDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
Janet M SilicianoDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
Robert SilicianoDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States.
James T StiversDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States.ORCID 0000-0003-2572-7807
Johns Hopkins University · USHoward Hughes Medical Institute · USUniversity of Colorado Denver · US

Funding

Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
Using NK Cells to eliminate the latent HIV reservoirU19AI096113 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI OTT, MELANIE MARIA · 2011 to 2015
$39.5M
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
Uracil Damage Recognition by Uracil DNA GlyocosylaseR01GM056834 · NIGMS · UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE · PI STIVERS, JAMES T. · 1998 to 2021
$8.3M
The Chemistry-Biology Interface Program at Johns Hopkins UniversityT32GM080189 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ROKITA, STEVEN E · 2008 to 2022
$3.5M
Immune Mechanisms of HIV-associated COPDU01HL121814 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KIRK, GREGORY D, MCDYER, JOHN F · 2013 to 2017
$3.5M
Fate of Invisible U/A Base Pairs Within HIV DNA in Myeloid Phagocytic CellsR01AI124777 · NIAID · JOHNS HOPKINS UNIVERSITY · PI STIVERS, JAMES T. · 2016 to 2020
$2.0M
Persistence and Fate of Invisible U/A Pairs in HIV-1 Proviral DNAR21AI112351 · NIAID · JOHNS HOPKINS UNIVERSITY · PI STIVERS, JAMES T. · 2014 to 2015
$317k
NHLBI NIH HHS U01 HL121814NIAID NIH HHS P30 AI094189NIAID NIH HHS R01 AI124777NIAID NIH HHS R21 AI112351NIAID NIH HHS U19 AI096109NIAID NIH HHS U19 AI096113NIGMS NIH HHS R01 GM056834NIGMS NIH HHS T32 GM080189
6 · The paper itself

Abstract

We report that a major subpopulation of monocyte-derived macrophages (MDMs) contains high levels of dUTP, which is incorporated into HIV-1 DNA during reverse transcription (U/A pairs), resulting in pre-integration restriction and post-integration mutagenesis. After entering the nucleus, uracilated viral DNA products are degraded by the uracil base excision repair (UBER) machinery with less than 1% of the uracilated DNA successfully integrating. Although uracilated proviral DNA showed few mutations, the viral genomic RNA was highly mutated, suggesting that errors occur during transcription. Viral DNA isolated from blood monocytes and alveolar macrophages (but not T cells) of drug-suppressed HIV-infected individuals also contained abundant uracils. The presence of viral uracils in short-lived monocytes suggests their recent infection through contact with virus producing cells in a tissue reservoir. These findings reveal new elements of a viral defense mechanism involving host UBER that may be relevant to the establishment and persistence of HIV-1 infection.

Indexed as

DNA RepairVirus IntegrationCells, CulturedDNA, ViralHIV-1HIV InfectionsHumansMacrophagesMutationReverse TranscriptionUracilDNA, ViralUracilhumanimmunologyinfectious diseaselatency in macrophagesmicrobiologyU/A DNA base pairs in HIVuracil base excision repairviral restriction

Identifiers

PMID27644592
PMCPMC5030084
OpenAlexW2523164178

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.