Evidence map›Paper›PMID 20924117›Full record

ArticleThe Journal of biological chemistry2010

Ribonucleoside triphosphates as substrate of human immunodeficiency virus type 1 reverse transcriptase in human macrophages.

Edward M Kennedy, Christina Gavegnano, Laura Nguyen, Rebecca Slater, Amanda Lucas, Emilie Fromentin, Raymond F Schinazi, Baek Kim

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

72 citing papers in PubMed, 102 citations in OpenAlex.

  1. Trial
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  12. Strain and rupture of HIV-1 capsids during uncoating.Proceedings of the National Academy of Sciences of the United States of America · 2022
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12 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 1 country.

Edward M KennedyDepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Christina Gavegnano
Laura Nguyen
Rebecca Slater
Amanda Lucas
Emilie Fromentin
Raymond F Schinazi
Baek Kim
University of Rochester Medical Center · USEmory University · USJohns Hopkins University Center for AIDS Research

Funding

Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Carlos del Rio · 2002 to 2026
$74.0M
Replication fidelity and lentiviral pathogenesisR01AI049781 · NIAID · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2002 to 2016
$4.9M
Synthesis and Biotransformation of Anti-HIV ProdrugsR37AI025899 · NIAID · UNIVERSITY OF GEORGIA (UGA) · PI CHU, CHUNG K · 2001 to 2010
$4.4M
The University of Rochester's Clinical and Translational Science InstituteTL1RR024135 · NCRR · UNIVERSITY OF ROCHESTER · PI PEARSON, THOMAS ARTHUR · 2006 to 2011
$3.7M
Training in Microbial PathogenesisT32AI007362 · NIAID · UNIVERSITY OF ROCHESTER · PI IGLEWSKI, BARBARA H. · 1990 to 2010
$2.6M
NUCLEOSIDES WITH DUAL ANTI-HIV AND HBV ACTIVITYR37AI041980 · NIAID · EMORY UNIVERSITY · PI SCHINAZI, RAYMOND FELIX · 2000 to 2009
$2.1M
Combination therapies for chronic HBV, liver disease and cancerR01AI076535 · NIAID · TEMPLE UNIV OF THE COMMONWEALTH · PI FEITELSON, MARK A · 2008 to 2012
$1.8M
Primate Model Towards HIV Eradication StrategiesR01OD011094 · OD · EMORY UNIVERSITY · PI NORTH, THOMAS W, SCHINAZI, RAYMOND FELIX · 2012 to 2012
$706k
Replicational Fidelity and Lentivial PathogenesisR56AI049781 · NIAID · EMORY UNIVERSITY · PI KIM, BAEK · 2017 to 2017
$390k
NCRR NIH HHS TL1 RR024135NIAID NIH HHS 2P30-AI-050409NIAID NIH HHS 5R37-AI-025899NIAID NIH HHS 5R37-AI-041980NIAID NIH HHS AI049781NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI049781NIAID NIH HHS R01 AI076535NIAID NIH HHS R01-AI-076535NIAID NIH HHS R37 AI025899NIAID NIH HHS R37 AI041980NIAID NIH HHS R56 AI049781NIAID NIH HHS T32 AI007362NIH HHS R01 OD011094
6 · The paper itself

Abstract

We biochemically simulated HIV-1 DNA polymerization in physiological nucleotide pools found in two HIV-1 target cell types: terminally differentiated/non-dividing macrophages and activated/dividing CD4(+) T cells. Quantitative tandem mass spectrometry shows that macrophages harbor 22-320-fold lower dNTP concentrations and a greater disparity between ribonucleoside triphosphate (rNTP) and dNTP concentrations than dividing target cells. A biochemical simulation of HIV-1 reverse transcription revealed that rNTPs are efficiently incorporated into DNA in the macrophage but not in the T cell environment. This implies that HIV-1 incorporates rNTPs during viral replication in macrophages and also predicts that rNTP chain terminators lacking a 3'-OH should inhibit HIV-1 reverse transcription in macrophages. Indeed, 3'-deoxyadenosine inhibits HIV-1 proviral DNA synthesis in human macrophages more efficiently than in CD4(+) T cells. This study reveals that the biochemical landscape of HIV-1 replication in macrophages is unique and that ribonucleoside chain terminators may be a new class of anti-HIV-1 agents specifically targeting viral macrophage infection.

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, ViralCD4-Positive T-LymphocytesChromatography, LiquidDNA PrimersHIV-1HIV Reverse TranscriptaseHumansKineticsMacrophagesNucleotidesProtein BindingRibonucleotidesU937 CellsDNA PrimersHIV Reverse TranscriptaseNucleotidesreverse transcriptase, Human immunodeficiency virus 1Ribonucleotides

Identifiers

PMID20924117
PMCPMC2998149
OpenAlexW2031476529

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.