A low pathogenic avian influenza A/Mallard/South Korea/KNU2019-34/2019 (H1N1) virus has the potential to increase the mammalian pathogenicity

This study assessed the pathogenicity of KNU19-34 (H1N1) AIV isolated from wild aquatic birds using mouse and ferret models. KNU19-34 caused high mortality in mice and exhibited severe extrapulmonary infection in the heart and kidneys. In ferrets, the virus replicated rapidly in both the upper and lower respiratory tracts. Similar to pandemic H1N1, KNU19-34 preferentially bound to α2,6-linked sialic acid receptors and replicated efficiently in human lung cells. Genetic analysis identified several novel amino acid mutations (PB2-L464M, HA-S92P, NP-G16S, and NP-T433I), suggesting KNU19-34’s potential for mammalian adaptation and cross-species transmission. These mutations, along with increased replication ability, indicate a higher likelihood of the virus infecting mammals.