ArticlePLoS pathogens2009
Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 86 citations in OpenAlex.
- RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction.The Journal of clinical investigation · 2014Trial
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- Structure-Guided Glycosylation of Hemagglutinin Enhances Stability and Modulates Immunogenicity of Influenza Vaccines.Vaccines · 2026Article
- Efficient replication of influenza D virus in the human airway underscores zoonotic potential.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Viral lineage and mode of exposure modulate within-host spatial dynamics of influenza A viruses in a guinea pig model.Journal of virology · 2026Article
- Efficient replication of influenza D virus in the human airway underscores zoonotic potential.bioRxiv : the preprint server for biology · 2026Article
- Viral lineage and mode of exposure modulate within host spatial dynamics of influenza A viruses.bioRxiv : the preprint server for biology · 2025Article
- Preferential apical infection and spread of human metapneumovirus highlights the importance of inhaled delivery of neutralizing monoclonal antibody to treat established infections.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hemagglutinin glycosylation pattern-specific effects: implications for the fitness of H9.4.2.5-branched H9N2 avian influenza viruses.Emerging microbes & infections · 2024Article
- Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.Influenza and other respiratory viruses · 2024Review
- Utility of HumanJournal of virology · 2023Article
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- Human Bocavirus 1 Infection of Well-Differentiated Human Airway Epithelium.Current protocols in microbiology · 2020Article
- Hemagglutinin Cleavability, Acid Stability, and Temperature Dependence Optimize Influenza B Virus for Replication in Human Airways.Journal of virology · 2019Article
- Alternative Experimental Models for Studying Influenza Proteins, Host-Virus Interactions and Anti-Influenza Drugs.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Tropism and Infectivity of a Seasonal A(H1N1) and a Highly Pathogenic Avian A(H5N1) Influenza Virus in Primary Differentiated Ferret Nasal Epithelial Cell Cultures.Journal of virology · 2019Article
- Sowing the Seeds of a Pandemic? Mammalian Pathogenicity and Transmissibility of H1 Variant Influenza Viruses from the Swine Reservoir.Tropical medicine and infectious disease · 2019Review
- Tissue tropisms opt for transmissible reassortants during avian and swine influenza A virus co-infection in swine.PLoS pathogens · 2018Article
- ComparativeJournal of virology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32 degrees C). These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40 degrees C), rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32 degrees C and 37 degrees C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32 degrees C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA) and neuraminidase (NA) from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and suggests that adaptation of avian influenza viruses to efficient infection at 32 degrees C may represent a critical evolutionary step enabling human-to-human transmission.
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