A few neutral glycans are regarded as virus receptors; however, a triple reassortant H1N1 human isolate, A/Iowa/1/06, has recently been shown to be able to bind to a complex-type N-glycan with terminal LacNAc. These neutral N-glycans were found in the porcine LY2157299 tracheal upper and lower parts and the porcine lungs with molar ratios of 8.9, 7.4 and 4.1, respectively. In contrast to neutral glycans, Sia with a negative charge is a major receptor and a host range determinant of influenza viruses. Two major entities that influence infectivity of influenza viruses are type and linkage of Sia. Two prevalent Sias found in mammalian cells were identified, but NeuAc was the predominant form in N-glycans of the porcine trachea and lungs. The NeuAc:NeuGc ratio varies among animal species and their tissues, 98:2 in the duck intestine and NeuGc accounting for more than 90% of Sia in epithelial cells of the horse trachea, whereas normal human tissues possess only NeuAc as they have a non-functional hydroxylase to produce NeuGc. The absence of NeuGc may protect humans from infection with some pathogens, such as enterotoxigenic Escherichia coli K99, but not from influenza viruses. Overall, both avian and human influenza A viruses appear to exhibit preference for NeuAc rather than NeuGc glycoconjugates. The third notuncommon Sia, 9-O-Ac-NeuAc, a primary receptor determinant of influenza C virus for infection of host cells, was not detected, indicating that this N-glycan either is not synthesized in the porcine trachea and lung or is present in other tissue. This is in agreement with the fact that influenza C viruses cause mild infection in the upper respiratory tract, although the presence of 9-O-Ac-NeuAc in the porcine trachea and lungs should not rule out the possibility that O-linked glycoproteins or glycolipids carry 9-O-Ac-NeuAc. The type of glycosidic linkage between Sia and Gal on the host cell surface is clearly the principal determinant of the host range restriction of influenza viruses: a2-3-linkage is avian virus preference, while a2-6-linkage is human virus preference. We found that there are gradually increased molar ratios of a2-6linked sialyl glycans compared to those of a2-3-linked sialyl glycans, 3.2-, 4.9- and 13.2–fold for NeuAc and 1.8-, 2.7- and 5.9fold for NeuGc in the upper trachea, lower trachea and lungs of the pig, respectively. Our data can explain why influenza viruses, both avian-like, classical swine and triple reassortant swine influenza viruses, replicated in pigs have changed in their receptor binding preference to human a2-6 receptor and have occasionally been isolated from humans. Our data also provide an explanation of why avian influenza virus before genetic change produced lower virus titers.