ArticleProceedings of the National Academy of Sciences of the United States of America2023
H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 21 citations in OpenAlex.
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- 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 · 2026Article
- Targeting virus-glycan recognition in influenza viruses and coronaviruses: from the molecular principles to glycomimetic antivirals strategies.RSC chemical biology · 2026Review
- Complete Blood Count-Derived Inflammatory Markers in Pediatric Lower Respiratory Tract Infection: A Narrative Review.Pathogens (Basel, Switzerland) · 2026Review
- Loss of hemagglutination ability by H3N2 influenza A virus, subclade K.bioRxiv : the preprint server for biology · 2026Article
- Dominant HA motif 131/132-NT shapes the phenotype of avian H9N2 influenza virus by modulating agglutination property, receptor specificity and infectivity in animals.Virologica Sinica · 2026Article
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- Automated Generation of Supported Lipid Bilayer Arrays with Controlled Receptor Densities in Well Plates.ACS applied materials & interfaces · 2026Article
- Combined network pharmacology and biological verification to investigate anti-influenza A virus effect and potential mechanism of Pudilan Xiaoyan Oral Liquid.Chinese herbal medicines · 2026Article
- Inferring context-specific site variation with evotuned protein language models.NAR genomics and bioinformatics · 2026Article
- Influenza virus infection during pregnancy: a review of risk factors, pathogenic mechanisms, and prevention strategies.Frontiers in immunology · 2026Review
- Intra-patient neuraminidase mutations in avian H5N1 influenza virus reduce sialidase activity to complement weaker hemagglutinin binding and facilitate human infection.PLoS pathogens · 2026Article
- Characterization of emerging H3N3 avian influenza viruses in poultry in China.Emerging microbes & infections · 2025Article
- Chronology of H3N2 human influenza virus surface glycoprotein adaptation from 1968 to 2019 reveals a surge of adaptation between 1997 and 2002.Journal of virology · 2025Article
- Epidemiological characteristics of influenza A virus infection across age groups: a longitudinal analysis based on gender and clinical diagnosis.Journal of translational medicine · 2025Article
- TfR1 facilitates influenza virus endocytosis and uncoating by interacting with NA and M1 via extracellular and intracellular domains.PLoS pathogens · 2025Article
- 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 · 2025Article
- Epistasis in the receptor-binding domain of contemporary H3N2 viruses that reverted to bind sialylated di-LacNAc repeats.Cell reports · 2025Article
- Virion motility of sialoglycan-cleaving respiratory viruses.Npj viruses · 2025Review
- Dynamic adaptation mutations and pathogenic characterization of a mouse-adapted seasonal human H3N2 influenza virus.Virology journal · 2025Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To become established upon zoonotic transfer, influenza A viruses (IAV) need to switch binding from "avian-type" α2-3-linked sialic acid receptors (2-3Sia) to "human-type" Siaα2-6-linked sialic acid receptors (2-6Sia). For the 1968 H3N2 pandemic virus, this was accomplished by two canonical amino acid substitutions in its hemagglutinin (HA) although a full specificity shift had not occurred. The receptor repertoire on epithelial cells is highly diverse and simultaneous interaction of a virus particle with a range of low- to very low-affinity receptors results in tight heteromultivalent binding. How this range of affinities determines binding selectivity and virus motility remains largely unknown as the analysis of low-affinity monovalent HA-receptor interactions is technically challenging. Here, a biolayer interferometry assay enabled a comprehensive analysis of receptor-binding kinetics evolution upon host-switching. Virus-binding kinetics of H3N2 virus isolates slowly evolved from 1968 to 1979 from mixed 2-3/2-6Sia specificity to high 2-6Sia specificity, surprisingly followed by a decline in selectivity after 1992. By using genetically tuned HEK293 cells, presenting either a simplified 2-3Sia- or 2-6Sia-specific receptor repertoire, receptor-specific binding was shown to correlate strongly with receptor-specific entry. In conclusion, the slow and continuous evolution of entry and receptor-binding specificity of seasonal H3N2 viruses contrasts with the paradigm that human IAVs need to rapidly acquire and maintain a high specificity for 2-6Sia. Analysis of the kinetic parameters of receptor binding provides a basis for understanding virus-binding specificity, motility, and HA/neuraminidase balance at the molecular level.
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