HAs of H1–H16 viruses recognize specific sialyl glycans on the host epithelial cell surface, as a crucial step mediating virus infection (Figure 3a). IAVs from avians, either wild birds or domestic birds, typically prefer the α2,3Sia terminal. Surprisingly, a recent study showed that some gull/tern H16 viruses prefer α2,6Neu5Ac over or equal to the α2,3Neu5Ac terminal of synthetic sialylglycopolymers [23]. It was suggested that the particularly distinctive receptor-binding specificity of H16 viruses may be related to their HAs containing A138S (found in human 1977-derived H1N1 viruses, reducing binding to α2,3Neu5Ac receptors) and E190T (the amino acid (aa) at position 190 determining binding specificity of H1N1 viruses to the sialyl linkage type) [23]. Usually, viruses adapt to bind to sialyl glycans dominant in the host target tissues. Information on virus collection from oral, nasal, nasopharyngeal, cloacal or feces swabs and sialyl glycan analysis of tissues of specific wild birds shedding the virus in the sample collection may lead to a better understanding of why some H16 viruses display binding distinct from that of other avian viruses. Binding preference for the internal part of sialyl glycans appears to differ among different viruses based on birds of isolation as indicated in Table 1.