Evidence map›Paper›PMID 30102740›Full record

ArticlePLoS pathogens2018

Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces.

Hongbo Guo, Huib Rabouw, Anne Slomp, Meiling Dai, Floor van der Vegt, Jan W M van Lent, Ryan McBride, James C Paulson, Raoul J de Groot, Frank J M van Kuppeveld and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
10.7field-weighted citation impact, top 1% 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

91 citing papers in PubMed, 143 citations in OpenAlex.

  1. Mucins and Respiratory Virus Infection.Annual review of virology · 2026
    Review
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  14. Enhanced visualization of influenza A virus entry into living cells using virus-view atomic force microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Review
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31 more citing papers are in PubMed but not listed here.

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 at 3 institutions in 2 countries.

Hongbo GuoVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0003-4593-2226
Huib RabouwVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Anne SlompVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Meiling DaiVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Floor van der VegtVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Jan W M van LentLaboratory of Virology, Wageningen University and Research, Droevendaalsesteeg 1, PB Wageningen, the Netherlands.
Ryan McBrideDepartments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0001-8616-1910
James C PaulsonDepartments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, Scripps Research Institute, La Jolla, California, United States of America.
Raoul J de GrootVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-2207-9472
Frank J M van KuppeveldVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Erik de VriesVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0003-0763-8202
Cornelis A M de HaanVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-4459-9874
Utrecht University · NLScripps Research Institute · USWageningen University & Research · NL

Funding

Influenza virus receptors on human airway epithelial cellsR01AI114730 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C · 2015 to 2023
$5.1M
NIAID NIH HHS R01 AI114730
6 · The paper itself

Abstract

Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors determine viral fitness and host tropism. Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor-repertoire. The crucial but poorly understood dynamics of these multivalent virus-receptor interactions cannot be properly analyzed using equilibrium binding models and endpoint binding assays. In this study, the use of biolayer interferometric analysis revealed the virtually irreversible nature of IAV binding to surfaces coated with synthetic sialosides or engineered sialoglycoproteins in the absence of NA activity. In addition to HA, NA was shown to be able to contribute to the initial binding rate while catalytically active. Virus-receptor binding in turn contributed to receptor cleavage by NA. Multiple low-affinity HA-SIA interactions resulted in overall extremely high avidity but also permitted a dynamic binding mode, in which NA activity was driving rolling of virus particles over the receptor-surface. Virus dissociation only took place after receptor density of the complete receptor-surface was sufficiently decreased due to NA activity of rolling IAV particles. The results indicate that in vivo IAV particles, after landing on the mucus layer, reside continuously in a receptor-bound state while rolling through the mucus layer and over epithelial cell surfaces driven by the HA-NA-receptor balance. Quantitative BLI analysis enabled functional examination of this balance which governs this dynamic and motile interaction that is expected to be crucial for penetration of the mucus layer and subsequent infection of cells by IAV but likely also by other enveloped viruses carrying a receptor-destroying enzyme in addition to a receptor-binding protein.

Indexed as

Virus AttachmentVirus InternalizationAnimalsCHO CellsCricetinaeCricetulusHEK293 CellsHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A virusKineticsNeuraminidaseProtein BindingReceptors, VirusHemagglutinin Glycoproteins, Influenza VirusNeuraminidaseReceptors, Virus

Identifiers

PMID30102740
PMCPMC6107293
OpenAlexW2886291741

What OpenQuestion holds

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LicenceCC BY
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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.