Research ArticleGenetics and biological property analysis of Korea lineage of influenza A H9N2 viruses

- Little information is available about the biological properties of H9N2 viruses of Y439 lineage in mammals.
- Some Korean H9N2 viruses caused higher than expected mortalities to mice without prior adaptation.
- Korean H9N2 with mammalian host-tropic mutations caused higher than expected mortalities to mice without prior adaptation.
- H9N2 viruses with enhanced pathogenicity to mice might have been established recently from endemic viruses.

H9N2 influenza viruses have been detected from wild and domestic avian species including chickens and ducks worldwide. Few studies have compared the biological properties of different H9N2 lineages or determined whether certain lineages might pose a higher risk to mammals, especially H9N2 viruses of Korean lineage. The objective of this study was to characterize the genetic and biological properties of 22 Korean H9N2 viruses and assess their potential risks to mammals. Their complete genomes were analyzed. Some Korean H9N2 viruses were found to carry mammalian host-specific mutations. Based on genomic diversities, these H9N2 viruses were divided into 12 genotypes. All 22 showed preferential binding to human-like receptor. Two of eight H9N2 viruses were highly lethal to mice, causing 90-100% mortality without prior adaptation and severe respiratory syndromes associated with diffuse lung injury, severe pneumonia, and alveolar damage. These findings suggest that recent Korean H9N2 viruses might have established a stable sublineage with enhanced pathogenicity to mice. Various H9N2 strains pathogenic to mice were endemic in wild bird, poultry farm, and live bird markets, suggesting that Korean H9N2 viruses could evolve to become a threat to humans. The findings emphasize the necessity of careful, continuous, and thorough surveillance paired with risk-assessment for circulating H9N2 influenza viruses.