Evidence map›Paper›PMID 33975931›Full record

ArticlemBio2021

Analysis of the Evolution of Pandemic Influenza A(H1N1) Virus Neuraminidase Reveals Entanglement of Different Phenotypic Characteristics.

Meiling Dai, Wenjuan Du, Carles Martínez-Romero, Tim Leenders, Tom Wennekes, Guus F Rimmelzwaan, Frank J M van Kuppeveld, Ron A M Fouchier, Adolfo Garcia-Sastre, Erik de Vries and 1 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
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

18 citing papers in PubMed, 20 citations in OpenAlex.

  1. Substitutions affecting the HA-NA-receptor balance preceded the emergence of the pandemic 2009 H1N1 virus.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Genomic evolution of influenza during the 2023-2024 season, the johns hopkins health system.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Plants (Basel, Switzerland) · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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

11 authors at 4 institutions in 3 countries.

Meiling Dai *Virology Section, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Wenjuan Du *Virology Section, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Carles Martínez-RomeroDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Tim LeendersDepartment Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
Tom WennekesDepartment Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
Guus F RimmelzwaanResearch Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany.
Frank J M van KuppeveldVirology Section, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Ron A M FouchierDepartment of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
Adolfo Garcia-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0002-6551-1827
Erik de VriesVirology Section, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Cornelis A M de HaanVirology Section, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands c.a.m.dehaan@uu.nl.ORCID 0000-0002-4459-9874
Utrecht University · NLIcahn School of Medicine at Mount Sinai · USErasmus MC · NLUniversity of Veterinary Medicine Hannover, Foundation · DE

Funding

NIAID NIH HHS HHSN272201400008C
6 · The paper itself

Abstract

The influenza A virus (IAV) neuraminidase (NA) is essential for virion release from cells and decoy receptors and an important target of antiviral drugs and antibodies. Adaptation to a new host sialome and escape from the host immune system are forces driving the selection of mutations in the NA gene. Phylogenetic analysis shows that until 2015, 16 amino acid substitutions in NA became fixed in the virus population after introduction in the human population of the pandemic IAV H1N1 (H1N1pdm09) in 2009. The accumulative effect of these substitutions, in the order in which they appeared, was analyzed using recombinant proteins and viruses in combination with different functional assays. The results indicate that NA activity did not evolve to a single optimum but rather fluctuated within a certain bandwidth. Furthermore, antigenic and enzymatic properties of NA were intertwined, with several residues affecting multiple properties. For example, the substitution K432E in the second sialic acid binding site, next to the catalytic site, was shown to affect catalytic activity, substrate specificity, and the pH optimum for maximum activity. This substitution also altered antigenicity of NA, which may explain its selection. We propose that the entanglement of NA phenotypes may be an important determining factor in the evolution of NA.

Indexed as

Evolution, MolecularPhenotypeAnimalsBinding SitesCells, CulturedDogsEpithelial CellsFemaleHEK293 CellsHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMadin Darby Canine Kidney CellsNeuraminidasePandemicsHemagglutinin Glycoproteins, Influenza VirusNeuraminidaseantigenicityenzymatic activityinfluenza A virusneuraminidase

Identifiers

PMID33975931
PMCPMC8262965
OpenAlexW3163749250

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.