Evidence map›Paper›PMID 40608831›Full record

ArticlePLoS pathogens2025

Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection.

Lonneke V Nouwen, Esther A Zaal, Inge Buitendijk, Marleen Zwaagstra, Chiara Aloise, Arno L W van Vliet, Jelle G Schipper, Alain van Mil, Celia R Berkers, Frank J M van Kuppeveld

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. 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
–field-weighted citation impact
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. 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

10 authors.

Lonneke V NouwenSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Esther A ZaalDivision Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Inge BuitendijkSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Marleen ZwaagstraSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Chiara AloiseSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Arno L W van VlietSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Jelle G SchipperSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Alain van MilExperimental Cardiology Laboratory, Department of Cardiology, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Celia R BerkersDivision Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Frank J M van KuppeveldSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0001-5800-749X

Funding

European Union’s Horizon 2024 ERC AdvancedInnovative Medicines Initiative 2 Joint Undertaking
6 · The paper itself

Abstract

Viruses, including picornaviruses, modulate cellular metabolism to generate sufficient building blocks for virus replication and dissemination. Previously, we showed that two picornaviruses, coxsackievirus B3 (CVB3) and EMCV, remodel nucleotide metabolism during infection. Here, we investigated whether this modulation is attributable to specific viral proteins. For this, we studied the modulation of metabolism by several recombinant CVB3 and EMCV viruses in HeLa cells. Using isotope tracing metabolomics with three distinct labels, 13C6-glucose or 13C5/15N2-glutamine, we reveal that the 2A protease of CVB3 and the Leader protein of EMCV inhibit de novo nucleotide synthesis. Furthermore, we show that nucleotide metabolism is also reprogrammed by CVB3 and EMCV in human induced pluripotent stem cell-derived cardiomyocytes. Our insights are important to increase understanding of picornavirus-host interactions and may lead to novel therapeutic strategies.

Indexed as

Encephalomyocarditis virusEnterovirus B, HumanNucleotidesPicornaviridaePicornaviridae InfectionsViral ProteinsCysteine EndopeptidasesHeLa CellsHumansMyocytes, CardiacVirus ReplicationCysteine EndopeptidasesNucleotidesViral Proteins

Identifiers

PMID40608831
PMCPMC12244537

What OpenQuestion holds

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LicenceCC BY
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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.