H9N2 avian influenza viruses (AIVs) have been isolated frequently from multiple avian species and, occasionally, from humans. To explore the potential molecular basis of cross-species transmission of H9N2 AIVs, an H9N2 AIV (A/chicken/Zhejiang/221/2016) was serially passaged in mouse lung. The results showed that the mouse-adapted H9N2 virus exhibited higher virulence and replicated more efficiently in mouse lung and liver. Whole-genome sequencing showed an amino acid substitution, D701N, in the PB2 protein, which is likely associated with the increased replicative ability of H9N2 virus in mice. The rapid emergence of adaptive substitutions indicates the necessity of continuous monitoring of H9N2 virus in poultry.
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This study was funded by grants from the National Science and Technology Major Project for the Control and Prevention of Major Infectious Diseases in China (2018ZX10711001, 2018ZX10102001, and 2020ZX10101016-004-002), Zhejiang Provincial Natural Science Foundation of China (LY19H260006), and the Independent Task of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (2022ZZ02).
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Supplementary Fig. S1 Location of the D701N substitution found in the PB2 protein of the mouse-adapted virus. The 3D crystal structure of polymerase PB2 (PDB ID: 6QPF) is shown; the green region represents the amino acid substitution at position 701. (PNG 368 kb)
Supplementary Fig. S2 Phylogenetic trees based on the eight genes of H9N2 avian influenza viruses. The A/chicken/Zhejiang/221/2016 (H9N2) virus is indicated by a black dot. The scale bar indicates the genetic distance between sequences. (PNG 136 kb)
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Yang, F., Zhang, X., Liu, F. et al. Rapid emergence of a PB2 D701N substitution during adaptation of an H9N2 avian influenza virus in mice. Arch Virol 167, 2299–2303 (2022). https://doi.org/10.1007/s00705-022-05536-1