Evidence map›Paper›PMID 34153286›Full record

ArticleJournal of molecular biology2021

Distinct Antiretroviral Mechanisms Elicited by a Viral Mutagen.

Megan Roth, Yumeng Z McDaniel, Michele B Daly, Nathaniel Talledge, Willie M Greggs, Steven E Patterson, Baek Kim, Louis M Mansky

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 56% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
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 2 institutions in 1 country.

Megan RothInstitute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Division of Basic Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Yumeng Z McDanielInstitute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Veterinary Medicine Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Michele B DalyCenter for Drug Discovery, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nathaniel TalledgeInstitute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Willie M GreggsInstitute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Comparative Molecular Biosciences Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Steven E PattersonInstitute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Center for Drug Design, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Baek KimCenter for Drug Discovery, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Louis M ManskyInstitute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Division of Basic Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Comparative Molecular Biosciences Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Veterinary Medicine Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Center for Drug Design, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address: mansky@umn.edu.
University of Minnesota · USEmory University · US

Funding

Training in PharmacoNeuroImmune Substance Abuse ResearchT32DA007097 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MOLITOR, THOMAS WILLIAM · 1985 to 2021
$13.1M
Comparative Medicine and Pathology TrainingT32OD010993 · OD · UNIVERSITY OF MINNESOTA · PI DAVID R BROWN, Cathy S. Carlson · 2012 to 2026
$6.2M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Lentivirus Replication Strategy and PathogenesisR01AI136581 · NIAID · EMORY UNIVERSITY · PI Baek Kim · 2018 to 2026
$3.9M
Minnesota Training Program in VirologyT32AI083196 · NIAID · UNIVERSITY OF MINNESOTA · PI Louis M Mansky · 2010 to 2026
$3.2M
Mechanisms of HIV-1 VariationR01GM056615 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MANSKY, LOUIS M. · 2003 to 2011
$2.6M
HIV Gag lattice morphology and particle biogenesisR01AI150468 · NIAID · UNIVERSITY OF MINNESOTA · PI MANSKY, LOUIS M., MUELLER, JOACHIM D · 2019 to 2020
$1.2M
Molecular Determinants of Retroviral Capsid Morphology using a Novel Imaging ApproachF32AI150351 · NIAID · UNIVERSITY OF MINNESOTA · PI TALLEDGE, NATHANIEL LEE · 2020 to 2021
$141k
NIAID NIH HHS F32 AI150351NIAID NIH HHS R01 AI136581NIAID NIH HHS R01 AI150468NIAID NIH HHS T32 AI083196NIDA NIH HHS T32 DA007097NIGMS NIH HHS R01 GM056615NIGMS NIH HHS R01 GM129325NIH HHS T32 OD010993
6 · The paper itself

Abstract

5-aza-cytidine (5-aza-C) has been shown to be a potent human immunodeficiency virus type 1 (HIV-1) mutagen that induces G-to-C hypermutagenesis by incorporation of the reduced form (i.e., 5-aza-dC, 5-aza-dCTP). Evidence to date suggests that this lethal mutagenesis is the primary antiretroviral mechanism for 5-aza-C. To investigate the breadth of application of 5-aza-C as an antiretroviral mutagen, we have conducted a comparative, parallel analysis of the antiviral mechanism of 5-aza-C between HIV-1 and gammaretroviruses - i.e., murine leukemia virus (MuLV) and feline leukemia virus (FeLV). Intriguingly, in contrast to the hallmark G-to-C hypermutagenesis observed with HIV-1, MuLV and FeLV did not reveal the presence of a significant increase in mutational burden, particularly that of G-to-C transversion mutations. The effect of 5-aza-dCTP on DNA synthesis revealed that while HIV-1 RT was not inhibited by 5-aza-dCTP even at 100 µM, 5-aza-dCTP was incorporated and significantly inhibited MuLV RT, generating pause sites and reducing the fully extended product. 5-aza-dCTP was found to be incorporated into DNA by MuLV RT or HIV-1 RT, but only acted as a non-obligate chain terminator for MuLV RT. This biochemical data provides an independent line of experimental evidence in support of the conclusion that HIV-1 and MuLV have distinct primary mechanisms of antiretroviral action with 5-aza-C. Taken together, our data provides striking evidence that an antiretroviral mutagen can have strong potency via distinct mechanisms of action among closely related viruses, unlinking antiviral activity from antiviral mechanism of action.

Indexed as

AnimalsAntiviral AgentsAzacitidineCatsCytidine TriphosphateHIVHIV InfectionsHumansLeukemia, ExperimentalLeukemia Virus, FelineLeukemia Virus, MurineMiceMutagenesisMutagensMutationRetroviridae Infections5-aza-2'-deoxycytidine-5'-triphosphateAntiviral AgentsAzacitidineCytidine TriphosphateMutagenscytosine analoggammaretroviruslentivirusmutagenesisretrovirus

Identifiers

PMID34153286
PMCPMC8380735
OpenAlexW3176977636

What OpenQuestion holds

Textmetadata
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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.