Selection of H3 avian influenza viruses with SAα2,6Gal receptor specificity in pigs

•Novel role of pigs in the generation of pandemic viruses are demonstrated.•H3 influenza viruses with human-type receptor specificity were selected in pigs.•Surveillance of swine influenza is important for the preparedness for pandemics.

Avian influenza viruses possess hemagglutinin (HA) which preferentially bind to the sialic acid α2,3-galactose sialyloligosaccharides (SAα2,3Gal) receptor. In contrast, human influenza viruses bind to sialic acid α2,6-galactose sialyloligosaccharides (SAα2,6Gal). The A/Hong Kong/68 (H3N2) virus preferentially binds to SAα2,6Gal, although its HA gene was derived from an avian influenza virus strain. To elucidate the mechanisms behind acquisition of binding specificity for the human-type receptor, the avian influenza virus, A/duck/Hokkaido/5/77 (H3N2), which carries the HA with SAα2,3Gal receptor specificity, was consecutively passaged in pigs. Viruses that preferentially bind to the SAα2,6Gal receptor were predominantly recovered from the nasal swabs of pigs after three passages. The present results indicate that avian influenza viruses can acquire the potential to infect humans after multiple infections in a pig population. Intensive surveillance of swine influenza is, thus, important for the preparedness for the future pandemics.