ArticlePLoS pathogens2016
Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses.
Article in PLoS pathogens, 2016. 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, 52 citations in OpenAlex.
- Investigation and impact of mammalian adaptation markers on H5N8 high pathogenicity avian influenza polymerase activity.Npj viruses · 2026Article
- PB1 mutations as key drivers of influenza A virus evolution.Frontiers in microbiology · 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
- Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential.Microbiology spectrum · 2025Article
- Chicken ANP32A-independent replication of highly pathogenic avian influenza viruses potentially leads to mammalian adaptation-related amino acid substitutions in viral PB2 and PA proteins.Journal of virology · 2025Article
- Influenza Virus Genomic Mutations, Host Barrier and Cross-species Transmission.Current genomics · 2025Review
- Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights.Emerging microbes & infections · 2024Article
- The host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region.PLoS pathogens · 2024Article
- Vaccination and Antiviral Treatment against Avian Influenza H5Nx Viruses: A Harbinger of Virus Control or Evolution.Vaccines · 2023Review
- Risk Assessment of the Possible Intermediate Host Role of Pigs for Coronaviruses with a Deep Learning Predictor.Viruses · 2023Article
- Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.PLoS pathogens · 2023Article
- Host-Pathogen Interactions Influencing Zoonotic Spillover Potential and Transmission in Humans.Viruses · 2023Review
- Article
- Adaptation to host cell environment during experimental evolution of Zika virus.Communications biology · 2022Article
- Modeling theBiomolecules · 2021Article
- PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range.Journal of virology · 2020Article
- H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity.Journal of virology · 2020Article
- Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections.Journal of virology · 2020Article
- Phenotypic Effects of Substitutions within the Receptor Binding Site of Highly Pathogenic Avian Influenza H5N1 Virus Observed during Human Infection.Journal of virology · 2020Article
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major determinant in the change of the avian influenza virus host range to humans is the E627K substitution in the PB2 polymerase protein. However, the polymerase activity of avian influenza viruses with a single PB2-E627K mutation is still lower than that of seasonal human influenza viruses, implying that avian viruses require polymerase mutations in addition to PB2-627K for human adaptation. Here, we used a database search of H5N1 clade 2.2.1 virus sequences with the PB2-627K mutation to identify other polymerase adaptation mutations that have been selected in infected patients. Several of the mutations identified acted cooperatively with PB2-627K to increase viral growth in human airway epithelial cells and mouse lungs. These mutations were in multiple domains of the polymerase complex other than the PB2-627 domain, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses. Thus, H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation.
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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.