Altered receptor-binding specificity of gull-adapted H13 avian influenza viruses corresponds to their unique host preferences

Avian influenza viruses (AIVs) recognize α2-3 sialosides as receptors. Previous studies showed that the structural diversity within α2-3 sialosides is related to the host specificity of AIVs. H13 AIVs are primarily isolated from gulls, although almost all AIV subtypes have been isolated from ducks, the natural hosts of AIVs. To elucidate the molecular basis of the host specificity of H13 viruses to gulls, the receptor-binding specificity of H13 hemagglutinins (HAs) and the distribution of viral receptors in gulls were investigated. The results revealed that recombinant HA (rHA) of H13 viruses had a binding preference for fucosylated α2-3 sialosides, which were distributed widely in the respiratory tract and intestines of gulls but not in the colon of ducks. Moreover, the receptor-binding specificity of mutant rHAs revealed that amino acids in the 130-loop and at position 227 of H13 HA were critical for the preference for fucosylated α2-3 sialosides. The results of the present study suggest that the binding specificity of H13 HA to fucosylated α2-3 sialosides is a key factor for the host susceptibility of H13 viruses to gulls.