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Receptor binding and cell entry In humans
the primary targets for influenza viruses are epithelial cells in the upper and lower respiratory tract. As indicated above, the viral HA binds to sialic acid residues on glycoproteins or glycolipids on the cell surface. The fine specificity of HA's receptor binding depends on the nature of the glycosidic linkage between the terminal sialic acid and the penultimate galactose residue on the receptor. Human influenza viruses preferentially bind to sialic acids attached to galactose in an α2,6 configuration, whereas avian viruses have a preference for sialic acids attached to galactose in an α2,3 linkage. This difference is thought to be the basis for the very inefficient transmission of avian influenza viruses to humans. Pigs, on the other hand, have receptors with either type of linkage between sialic acid and galactose, and thus are readily susceptible to infection with both human and avian viruses. Co-infection of pigs with different influenza viruses is considered one mechanism by which new influenza viruses with pandemic potential may arise
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