Evidence map›Paper›PMID 41818353›Full record

ArticleScience (New York, N.Y.)2026

Polymerase trapping as the mechanism of H5 highly pathogenic avian influenza virus genesis.

Mathis Funk, Monique I Spronken, Roy M Hutchinson, Benoit Arragain, Pauline Juyoux, Theo M Bestebroer, Anja C M de Bruin, Alexander P Gultyaev, Ron A M Fouchier, Stephen Cusack and 2 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

12 authors.

Mathis FunkDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.ORCID 0000-0001-7830-9989
Monique I SpronkenDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.ORCID 0009-0009-5613-0705
Roy M HutchinsonDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.
Benoit ArragainEuropean Molecular Biology Laboratory, EMBL Grenoble, Grenoble, France.ORCID 0000-0002-5593-4682
Pauline JuyouxUniversity Grenoble Alpes, CNRS, CEA, EMBL, Grenoble, France.ORCID 0000-0003-3153-1376
Theo M BestebroerDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.
Anja C M de BruinDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.ORCID 0000-0001-5202-4475
Alexander P GultyaevDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.
Ron A M FouchierDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.ORCID 0000-0001-8095-2869
Stephen CusackEuropean Molecular Biology Laboratory, EMBL Grenoble, Grenoble, France.ORCID 0000-0002-9324-0796
Aartjan J W Te VelthuisLewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID 0000-0002-5129-3953
Mathilde RichardDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.ORCID 0000-0003-0240-9312

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00014 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2021 to 2025
$62.6M
Structure and dynamics of RNA elements regulating viral aberrant RNA synthesisDP2AI175474 · NIAID · PRINCETON UNIVERSITY · PI TE VELTHUIS, AREND JAN · 2022 to 2025
$2.4M
Unravelling highly pathogenic influenza virus emergenceR01AI177487 · NIAID · ERASMUS MEDICAL CENTER · PI Mathilde Richard · 2023 to 2026
$1.5M
NIAID NIH HHS 75N93021C00014NIAID NIH HHS DP2 AI175474NIAID NIH HHS R01 AI177487NIH HHS HHSN272201400008C
6 · The paper itself

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) derive from H5 and H7 low pathogenic avian influenza viruses (LPAIVs). Although insertion of a furin-cleavable multibasic cleavage site (MBCS) in the hemagglutinin gene was identified decades ago as the genetic basis for the LPAIV-to-HPAIV transition, the mechanisms underlying the occurrence of insertion are unknown. Here, we show that transient H5 RNA structures, predicted to trap the influenza virus polymerase on purine-rich sequences, drive nucleotide insertions, providing empirical evidence of RNA structure involvement in MBCS acquisition. Introduction of H5-like sequences and structures into an H6 hemagglutinin resulted in MBCS-yielding insertions. Our results show that nucleotide insertions that underlie H5 HPAIV emergence result from an RNA structure-driven diversity-generating mechanism, which could also occur in other RNA viruses.

Indexed as

Hemagglutinin Glycoproteins, Influenza VirusInfluenza A virusInfluenza A Virus, H5N1 SubtypeMutagenesis, InsertionalRNA-Dependent RNA PolymeraseRNA, ViralAnimalsBirdsFurinInfluenza in BirdsNucleic Acid ConformationVirulenceFurinhemagglutinin, avian influenza A virusHemagglutinin Glycoproteins, Influenza VirusRNA-Dependent RNA PolymeraseRNA, Viral

Identifiers

PMID41818353
PMCPMC12987535

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Registered trials

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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.