BioProject

Sporadic human infections of avian influenza virus (AIV) raise concern of its public health risk. More...

Sporadic human infections of avian influenza virus (AIV) raise concern of its public health risk. To reveal substitutions that associated with receptor binding preference and host adaptation of H9N2, here, we generated a virus library with random mutations in HA gene. When the virus library was passaged in vivo, the wild-type strain and deltaL226/R229I which prefer Sia-a2,3 were dominant in chickens and mice. While virus with N289D substitution which prefer Sia-a2,6 was enriched during passaging in ferrets. This is consistent with the predominance of Sia-a2,6 in respiratory tract epithelial cells of ferrets. The infection of deltaL226/R229I virus in mice increased expression levels of TNF signaling pathways that may promote the development of the cytokine release syndrome, which explain its higher fatality rate. In conclusion, based on random mutagenesis of the HA gene, this study identifies key substitutions that influence the interspecific transmission potential of the H9N2 influenza virus. Less...