“…Terminal sialic acid linkage to the penultimate sugar of the glycan chain occurs via carbon 3 or carbon 6, giving the two isomers ␣-2,3 and ␣-2,6 SA, respectively (32). The human upper respiratory tract, the primary site of influenza virus replication in the human host, has abundant SA of the ␣-2,6 isomer, while in the avian gut, the site of replication in avian hosts, the ␣-2,3 conformer predominates, as demonstrated by isoform-specific lectin staining (22,23,38). Among a variety of factors that influence tropism, a major host adaptation facilitating avian influenza virus infection and transmission among humans is mutation in the receptor binding pocket of the HA protein to allow efficient ␣-2,6 SA rather than ␣-2,3 SA binding (19,21,33).…”