Human trachea primary epithelial cells express both sialyl(α2-3)Gal receptor for human parainfluenza virus type 1 and avian influenza viruses, and sialyl(α2-6)Gal receptor for human influenza viruses

We reported previously that the dominant receptors of influenza A and B viruses, and human and murine respiroviruses, were sialylglycoproteins and gangliosides containing monosialo-lactosamine type I-and II-residues, such as sialic acid-alpha 2-3(6)-Gal beta 1-3(4)-GlcNAc beta 1-. In addition, the Sia alpha 2-3Gal linkage was predominantly recognized by avian and horse influenza viruses, and human parainfluenza virus type 1 (hPIV-1), whereas the Sia alpha 2-6Gal linkage was mainly recognized by human influenza viruses (Paulson JC in "The Receptors'' [Conn M Ed] 2, 131-219 (1985); Suzuki Y, Prog Lipid Res 33, 429-57 (1994); Ito T, J Virol 73, 6743-51 (2000); Suzuki Y, J Virol 74, 11825-31 (2000); Suzuki T, J. Virol 75, 4604-4613 (2001); Suzuki Y, Biol. Pharm. Bull. 28, 399-408 (2005)). To clarify the distribution of influenza virus receptors on the human bronchial epithelium cell surface, we investigated a primary culture of normal human bronchial epithelial (NHBE) cells using two types of lectin (MAA and SNA), which recognize sialyl linkages (alpha 2-3 and alpha 2-6), using fluorescence-activated cell-sorting analysis. The results showed that both alpha 2-3- and alpha 2-6-linked Sias were expressed on the surface of primary human bronchial epithelial cells. The cells infected by hPIV-1 bound to MAA, confirming that cells targeted by hPIV-1 have alpha 2-3-linked oligosaccharides. We also compared the ability of hPIV-1 and human influenza A virus to infect primary human bronchial epithelial cells pre-treated with Sia alpha 2-3Gal-specific sialidase from Salmonella typhimurium. No difference was observed in the number of sialidase pre-treated and non-treated cells infected with human influenza A virus, which binds to Sia alpha 2-6Gal-linked oligosaccharides. By contrast, the number of cells infected with hPIV-1 decreased significantly upon sialidase treatment. Thus, cultured NHBE cells showed both alpha 2-3-linked Sias recognized by hPIV-1 and avian influenza virus receptors, and alpha 2-6-linked Sias recognized by human influenza virus receptors.