Evidence map›Paper›PMID 41662385›Full record

ArticlePLoS pathogens2026

Flexibility and modulation of translation initiation in enterovirus genomes.

Rhian L O'Connor, Georgia M Cook, Jacqueline Hankinson, Ksenia Fominykh, Samantha H Cheng, Daniel A Nash, Aurélie Cenier, Komal M Nayak, Stephen C Graham, Janet E Deane and 3 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

13 authors.

Rhian L O'ConnorDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Georgia M CookDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Jacqueline HankinsonDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Ksenia FominykhDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Samantha H ChengDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Daniel A NashDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Aurélie CenierCambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Komal M NayakCambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Stephen C GrahamDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Janet E DeaneCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Matthias ZilbauerCambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Andrew E FirthDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Valeria LullaDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID https://orcid.org/0000-0002-6605-0727

Funding

Wellcome Trust
6 · The paper itself

Abstract

Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. Additionally, we demonstrate regulation of uORF translation in response to stress. These findings reveal the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems.

Indexed as

EnterovirusGenome, ViralPeptide Chain Initiation, TranslationalAnimalsCodon, InitiatorHumansOpen Reading FramesProtein BiosynthesisRibosome ProfilingCodon, Initiator

Identifiers

PMID41662385
PMCPMC12904569

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.