ArticleVirologica Sinica2023
Enhanced pathogenicity and transmissibility of H9N2 avian influenza virus in mammals by hemagglutinin mutations combined with PB2-627K.
Article in Virologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 25 citations in OpenAlex.
- Molecular epidemiological characteristics of H9N2 subtype avian influenza virus in the external environment of western Zhejiang, China, 2014-2025.Frontiers in public health · 2026Article
- Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus.Emerging microbes & infections · 2025Article
- Molecular and ecological determinants of mammalian adaptability in avian influenza virus.Infection · 2025Review
- E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus.Veterinary research · 2025Article
- Emerging zoonotic potential of H4N1 avian influenza virus: enhanced human receptor binding and replication via novel mutations.Virology journal · 2025Article
- Random forest algorithm reveals novel sites in HA protein that shift receptor binding preference of the H9N2 avian influenza virus.Virologica Sinica · 2025Article
- Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice.Veterinary research · 2024Article
- Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation.Viruses · 2024Review
- Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice.Infectious medicine · 2024Article
- Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice.Virologica Sinica · 2024Article
- Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication.Virologica Sinica · 2024Article
- Genetics and Pathogenicity of Influenza A (H4N6) Virus Isolated from Wild Birds in Jiangsu Province, China, 2023.Transboundary and emerging diseases · 2024Article
- Construction and Immunogenicity Evaluation of Recombinant Bacillus subtilis Expressing HA1 Protein of H9N2 Avian Influenza Virus.Current microbiology · 2023Article
- Pathogenicity and virulence of influenza.Virulence · 2023Review
- Genetically Related Avian Influenza H7N9 Viruses Exhibit Different Pathogenicity in Mice.Animals : an open access journal from MDPI · 2023Article
- Reported human infections of H9N2 avian influenza virus in China in 2021.Frontiers in public health · 2023Article
- Pathogenicity and Transmissibility of Clade 2.3.4.4h H5N6 Avian Influenza Viruses in Mammals.Animals : an open access journal from MDPI · 2022Article
- Pathogenicity and Transmissibility of Goose-Origin H5N6 Avian Influenza Virus Clade 2.3.4.4h in Mammals.Viruses · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
H9N2 avian influenza viruses (AIVs) circulate globally in poultry and have become the dominant AIV subtype in China in recent years. Previously, we demonstrated that the H9N2 virus (A/chicken/Eastern China/SDKD1/2015) naturally harbors a mammalian-adaptive molecular factor (627K) in the PB2 protein and is weakly pathogenic in mice. Here, we focused on new markers for virulence in mammals. A mouse-adapted H9N2 virus was serially passaged in mice by infecting their lungs. As expected, infected mice showed clinical symptoms and died at passage six. A comparison between the wild-type and mouse-adapted virus sequences identified amino acid substitutions in the hemagglutinin (HA) protein. H9N2 viruses with the T187P + M227L double mutation exhibited an increased affinity to human-type (SAα2,6Gal) receptors and significantly enhanced viral attachment to mouse lung tissues, which contributed to enhancing viral replication and virulence in mice. Additionally, HA with the T187P + M227L mutation enabled H9N2 viral transmission in guinea pigs via direct contact. AIV pathogenicity in mice is a polygenic trait. Our results demonstrated that these HA mutations might be combined with PB2-627K to significantly increase H9N2 virulence in mice, and this enhanced virulence was achieved in other H9N2 AIVs by generating the same combination of mutations. In summary, our study identified novel key elements in the HA protein that are required for H9N2 pathogenicity in mice and provided valuable insights into pandemic preparedness against emerging H9N2 strains.
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