Genesis and biological features of H7 avian influenza viruses in migratory birds and implications for cross-species infection

H7 subtype avian influenza viruses (AIVs) pose a potential pandemic risk, as they can cause poultry outbreaks and spill over to mammals. H7 viruses harboured by migratory birds are recognized as progenitors of poultry and mammalian strains and remain incompletely characterized. In this study, we characterized the genetic and biological features of the H7N2 and H7N4 viruses circulating in migratory birds sampled between 2017 and 2024 in eastern China. We found that wild bird-derived H7 viruses are carried primarily by species of Anatidae, Phasianidae , and Scolopacidae and exhibit considerable genetic diversity. Moreover, the H7N2 and H7N4 viruses can infect domestic birds, as evidenced by their replication and viral shedding in ducks and chickens. Importantly, these viruses replicated efficiently in mice without prior adaptation, and the rapid emergence of mammalian-adapted mutants was detected in inoculated mice at 9 or 11 days post-inoculation. Further analyses revealed that the PB2-E627K substitution played a critical role in increasing the replication and virulence of the mouse-adapted mutants, whereas the HA-G205E and HA-E393K substitutions affected viral stability. These findings highlight the importance of strengthening surveillance at the wild bird–domestic poultry interface and reducing mammalian exposure to avian species to prepare for the potential risks posed by H7 viruses.