ArticlePLoS pathogens2019
The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- Paramyxovirus infection driven by heteromultivalent sialoglycotope binding.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evolution, spread and impact of highly pathogenic H5 avian influenza A viruses.Nature reviews. Microbiology · 2026Review
- Identification of β4GALNT2 as an anti-hPIV3 factor through genome-wide CRISPR/Cas9 library screening.Emerging microbes & infections · 2025Article
- Selective labeling and visualization of viral and bacterial neuraminidases usingRSC chemical biology · 2025Article
- Cell-based sialoglycan arrays for directly comparing influenza A virus receptor requirements for binding and infection.iScience · 2025Article
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
- Unraveling dynamics of paramyxovirus-receptor interactions using nanoparticles displaying hemagglutinin-neuraminidase.PLoS pathogens · 2024Article
- Highly pathogenic avian influenza A(H5N1) virus infections on fur farms connected to mass mortalities of black-headed gulls, Finland, July to October 2023.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2024Article
- Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation.Viruses · 2024Review
- Receptor Binding Properties of Neuraminidase for influenza A virus: An Overview of Recent Research Advances.Virulence · 2023Review
- H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Kinetic analysis of paramyxovirus-sialoglycan receptor interactions reveals virion motility.PLoS pathogens · 2023Article
- Phenotypic effects of mutations observed in the neuraminidase of human origin H5N1 influenza A viruses.PLoS pathogens · 2023Article
- Varying Viral Replication and Disease Profiles of H2N2 Influenza in Ferrets Is Associated with Virus Isolate and Inoculation Route.Journal of virology · 2022Article
- Human-type sialic acid receptors contribute to avian influenza A virus binding and entry by hetero-multivalent interactions.Nature communications · 2022Article
- Binding mechanism of oseltamivir and influenza neuraminidase suggests perspectives for the design of new anti-influenza drugs.PLoS computational biology · 2022Article
- Applications of Surface Plasmon Resonance and Biolayer Interferometry for Virus-Ligand Binding.Viruses · 2022Review
- Selection of an Optimal Recombinant Egyptian H9N2 Avian Influenza Vaccine Strain for Poultry with High Antigenicity and Safety.Vaccines · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2nd sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein.
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