ArticleJournal of virology2012
Decreased neuraminidase activity is important for the adaptation of H5N1 influenza virus to human airway epithelium.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- In silico analysis of pH stabilising mutations of hemagglutinin of influenza A virus H5N1 clade 2.3.4.4b.Npj viruses · 2026Review
- Evolution of H5N1 Cross-Species Transmission: Adaptive Mutations Driving Avian-to-Human Infection.Advanced genetics (Hoboken, N.J.) · 2026Article
- Intra-patient neuraminidase mutations in avian H5N1 influenza virus reduce sialidase activity to complement weaker hemagglutinin binding and facilitate human infection.PLoS pathogens · 2026Article
- Host cell entry receptors as pharmacological targets in respiratory viral infections: from biology to clinical translation.Frontiers in cellular and infection microbiology · 2026Review
- Virion motility of sialoglycan-cleaving respiratory viruses.Npj viruses · 2025Review
- The sweet side of H5N1 influenza virus infection.PLoS pathogens · 2025Article
- Influenza neuraminidase mutations and resistance to neuraminidase inhibitors.Emerging microbes & infections · 2024Review
- A computational approach to design a multiepitope vaccine against H5N1 virus.Virology journal · 2024Article
- Phenotypic effects of mutations observed in the neuraminidase of human origin H5N1 influenza A viruses.PLoS pathogens · 2023Article
- Insight into the first multi-epitope-based peptide subunit vaccine against avian influenza A virus (H5N6): An immunoinformatics approach.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2022Article
- Influenza A Virus Agnostic Receptor Tropism Revealed Using a Novel Biological System with Terminal Sialic Acid Knockout Cells.Journal of virology · 2022Article
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- H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity.Journal of virology · 2020Article
- A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses.Journal of virology · 2019Article
- Alternative Experimental Models for Studying Influenza Proteins, Host-Virus Interactions and Anti-Influenza Drugs.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Generation and characterization of interferon-lambda 1-resistant H1N1 influenza A viruses.PloS one · 2017Article
- Impact of a large deletion in the neuraminidase protein identified in a laninamivir-selected influenza A/Brisbane/10/2007 (H3N2) variant on viral fitness in vitro and in ferrets.Influenza and other respiratory viruses · 2016Article
- Vaccine Design for H5N1 Based on B- and T-cell Epitope Predictions.Bioinformatics and biology insights · 2016Article
- Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Highly pathogenic avian H5N1 influenza viruses remain a pandemic threat. Antiviral drugs such as neuraminidase (NA) inhibitors will be crucial for disease control in the event of a pandemic. Should drug-resistant H5N1 viruses develop, all defense strategies will be compromised. To determine the likelihood and mechanisms of emergence of NA inhibitor-resistant H5N1 variants in humans, we serially passaged two H5N1 viruses, A/Hong Kong/213/03 and A/Turkey/65-1242/06, in normal human bronchial epithelial (NHBE) cells in the presence of oseltamivir, zanamivir, or peramivir. To monitor the emergence of changes associated with the adaptation of H5N1 viruses to humans, we passaged the strains in the absence of drugs. Under pressure of each NA inhibitor, A/Turkey/65-1242/06 developed mutations in the hemagglutinin (HA) (H28R and P194L/T215I) and NA (E119A) proteins that reduced virus binding to α2,3-sialyl receptor and NA activity. Oseltamivir pressure selected a variant of A/Hong Kong/213/03 virus with HA P194S mutation that decreased viral binding to α2,6 receptor. Under peramivir pressure, A/Hong Kong/213/03 virus developed a novel NA mutation, R156K, that reduced binding to all three drugs, caused about 90% loss of NA activity, and compromised replication in NHBE cells. Both strains were eliminated in NHBE cells when they were cultivated in the absence of drugs. Here, we show for the first time that decreased NA activity mediated through NA inhibitors is essential for the adaptation of pandemic H5N1 influenza virus to humans. This ability of decreased NA activity to promote H5N1 infection underlines the necessity to optimize management strategies for a plausible H5N1 pandemic.
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Registered trials
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.