Evidence map›Paper›PMID 40875754›Full record

ArticlePLoS pathogens2025

The multifaceted role of the viral 2A protease in enterovirus replication and antagonism of host antiviral responses.

Jelle G Schipper, Chiara Aloise, Sereina O Sutter, Marleen Zwaagstra, Arno L W van Vliet, Rana Abdelnabi, Bob Ignacio, Kimberly M Bonger, Dagmar Roelofs, Judith M A van den Brand and 6 more

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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. 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

16 authors.

Jelle G SchipperSection of Virology, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Chiara AloiseSection of Virology, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Sereina O SutterSection of Virology, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Marleen ZwaagstraSection of Virology, Division of Infectious Diseases and 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 and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Rana AbdelnabiDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology, Antiviral Drug & Vaccine Research Group, KU Leuven, Leuven, Belgium.
Bob IgnacioDepartment of Synthetic Organic Chemistry, Chemical Biology Lab, Radboud University, Nijmegen, the Netherlands.
Kimberly M BongerDepartment of Synthetic Organic Chemistry, Chemical Biology Lab, Radboud University, Nijmegen, the Netherlands.
Dagmar RoelofsDivision of Pathology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Judith M A van den BrandDivision of Pathology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Richard W WubboltsCenter for Cell Imaging, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Lucas J M BruursOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.
Hendrik Jan ThibautDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology, Antiviral Drug & Vaccine Research Group, KU Leuven, Leuven, Belgium.
Johan NeytsDepartment of Microbiology, Immunology and Transplantation, Rega Institute, Virology, Antiviral Drug & Vaccine Research Group, KU Leuven, Leuven, Belgium.
Marvin E TanenbaumOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.
Frank J M van KuppeveldSection of Virology, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0001-5800-749X

Funding

Belgian Federal Government for the VirusBank PlatformEuropean Commission (EC) Marie Sklodowska-Curie Actions (MSCA) Innovative Training NetworkOncode Institute
6 · The paper itself

Abstract

Enteroviruses dramatically remodel the cellular infrastructure for efficient replication and curtailing host antiviral responses. The roles of viral proteins in these processes have been studied mostly in vitro, by ectopic overexpression, or by surrogate infection systems, all of which have shortcomings. Here, we replace the essential 2A cleavage site at the P1-P2 junction with an internal ribosome entry site (IRES), 3CD cleavage site, or T2A sequence, allowing us to catalytically inactivate 2Apro in the virus context. Viruses with an inactive 2Apro are hampered in replication in cell lines and are severely attenuated in a Coxsackievirus B3 (CVB3) mouse pancreatitis infection model. We show that 2Apro is essential for disturbing nucleocytoplasmic transport, shutting down host mRNA translation, suppressing stress granule formation, suppressing the induction of the IFN response, and overcoming IFN-induced restriction factors. Moreover, using an advanced single-molecule live cell imaging approach, we reveal that 2Apro is important for the initial round of replication of the incoming viral RNA, which is a bottleneck for efficient infection. Thus, 2Apro plays a critical role in subverting antiviral responses and establishing a favorable environment to expedite enterovirus replication.

Indexed as

Coxsackievirus InfectionsCysteine EndopeptidasesEnterovirusEnterovirus B, HumanEnterovirus InfectionsViral ProteinsVirus ReplicationAnimalsHost-Pathogen InteractionsHumansMiceCysteine Endopeptidasespicornain 2A, PicornavirusViral Proteins

Identifiers

PMID40875754
PMCPMC12410887

What Socratic 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 Socratic graph.