Evidence map›Paper›PMID 39609576›Full record

ArticleNature microbiology2025

Deep mutation, insertion and deletion scanning across the Enterovirus A proteome reveals constraints shaping viral evolution.

William Bakhache, Walker Symonds-Orr, Lauren McCormick, Patrick T Dolan

Abstract read
In one paragraph

Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Open questions in enterovirus uncoating.Journal of virology · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Reporter-expressing viruses for antiviral drug discovery research.Frontiers in cellular and infection microbiology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

William BakhacheQuantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2047-4866
Walker Symonds-OrrQuantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.
Lauren McCormickQuantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4928-3008
Patrick T DolanQuantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA. patrick.dolan@nih.gov.ORCID http://orcid.org/0000-0002-4169-0058

Funding

Virus evolution and host responses in positive-sense RNA virusesZIAAI001360 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOLAN, PATRICK · 2022 to 2025
$7.4M
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) 1ZIAA001360Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) 1ZIAAI001360Intramural NIH HHS ZIA AI001360
6 · The paper itself

Abstract

Insertions and deletions (InDels) are essential to protein evolution. In RNA viruses, InDels contribute to the emergence of viruses with new phenotypes, including altered host engagement and tropism. However, the tolerance of viral proteins for InDels has not been extensively studied. Here, we conduct deep mutational scanning to map and quantify the mutational tolerance of a complete viral proteome to insertion, deletion and substitution. We engineered approximately 45,000 insertions, 6,000 deletions and 41,000 amino acid substitutions across the nearly 2,200 coding positions of the Enterovirus A71 proteome, quantifying their effects on viral fitness by population sequencing. The vast majority of InDels are lethal to the virus, tolerated at only a few hotspots. Some of these hotspots overlap with sites of host recognition and immune engagement, suggesting tolerance at these sites reflects the important role InDels have played in the past phenotypic diversification of Enterovirus A.

Indexed as

Enterovirus A, HumanEvolution, MolecularINDEL MutationProteomeViral ProteinsAmino Acid SubstitutionHumansMutagenesis, InsertionalSequence DeletionProteomeViral Proteins

Identifiers

PMID39609576
PMCPMC11726453

What OpenQuestion holds

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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.