ArticleJournal of virology2017
Mutation of the Second Sialic Acid-Binding Site, Resulting in Reduced Neuraminidase Activity, Preceded the Emergence of H7N9 Influenza A Virus.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 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
- The receptor landscape of influenza A viruses.Journal of virology · 2026Review
- Characterization of the glycoproteins of fish and amphibian influenza B-like viruses.Science advances · 2025Article
- A Review of Cross-Species Transmission Mechanisms of Influenza Viruses.Veterinary sciences · 2025Review
- Unraveling dynamics of paramyxovirus-receptor interactions using nanoparticles displaying hemagglutinin-neuraminidase.PLoS pathogens · 2024Article
- Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation.Viruses · 2024Review
- Unveiling the Potent Antiviral and Antioxidant Activities of an Aqueous Extract fromFoods (Basel, Switzerland) · 2023Article
- Receptor Binding Properties of Neuraminidase for influenza A virus: An Overview of Recent Research Advances.Virulence · 2023Review
- Avian Influenza Virus Tropism in Humans.Viruses · 2023Review
- Binding mechanism of oseltamivir and influenza neuraminidase suggests perspectives for the design of new anti-influenza drugs.PLoS computational biology · 2022Article
- Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors.Journal of medicinal chemistry · 2022Article
- Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus.Nature communications · 2021Article
- Second sialic acid-binding site of influenza A virus neuraminidase: binding receptors for efficient release.The FEBS journal · 2021Article
- H7N9 Influenza Virus in China.Cold Spring Harbor perspectives in medicine · 2021Review
- Article
- Avian Influenza H7N9 Virus Adaptation to Human Hosts.Viruses · 2021Article
- Multiscale Simulations Examining Glycan Shield Effects on Drug Binding to Influenza Neuraminidase.Biophysical journal · 2020Article
- Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mutation of the second sialic acid-binding site of influenza A virus neuraminidase drives compensatory mutations in hemagglutinin.PLoS pathogens · 2020Article
- Evolution and Adaptation of the Avian H7N9 Virus into the Human Host.Microorganisms · 2020Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The emergence of the novel influenza A virus (IAV) H7N9 since 2013 has caused concerns about the ability of the virus to spread between humans. Analysis of the receptor-binding properties of the H7 protein of a human isolate revealed modestly increased binding to α2,6 sialosides and reduced, but still dominant, binding to α2,3-linked sialic acids (SIAs) compared to a closely related avian H7N9 virus from 2008. Here, we show that the corresponding N9 neuraminidases (NAs) display equal enzymatic activities on a soluble monovalent substrate and similar substrate specificities on a glycan array. In contrast, solid-phase activity and binding assays demonstrated reduced specific activity and decreased binding of the novel N9 protein. Mutational analysis showed that these differences resulted from substitution T401A in the 2nd SIA-binding site, indicating that substrate binding via this site enhances NA catalytic activity. Substitution T401A in the novel N9 protein appears to functionally mimic the substitutions that are found in the 2nd SIA-binding site of NA proteins of avian-derived IAVs that became human pandemic viruses. Our phylogenetic analyses show that substitution T401A occurred prior to substitutions in hemagglutinin (HA), causing the altered receptor-binding properties mentioned above. Hence, in contrast to the widespread assumption that such changes in NA are obtained only after acquisition of functional changes in HA, our data indicate that mutations in the 2nd SIA-binding site may have enabled and even driven the acquisition of altered HA receptor-binding properties and may have contributed to the spread of the novel H7N9 viruses.
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