INFLUENZA-VIRUS STRAINS SELECTIVELY RECOGNIZE SIALYLOLIGOSACCHARIDES ON HUMAN RESPIRATORY EPITHELIUM - THE ROLE OF THE HOST-CELL IN SELECTION OF HEMAGGLUTININ RECEPTOR SPECIFICITY

The complement of sialyloligosaccharides present on the surface of hum an tracheal epithelium has been implicated as an important factor in t he selection of hemagglutinin receptor specificity of human influenza A virus. Human strains of influenza A virus preferentially recognize h ost cell receptors bearing SAalpha2,6Gal sequences, a sequence which i s found on the surface of ciliated tracheal epithelium. A fluorescentl y-labelled H3 human virus strain bound avidly to the apical surface of human tracheal epithelium, while a fluorescently-labelled receptor va riant strain, which preferentially binds SAalpha2,3Gal sequences, show ed little binding to the epithelial surface and localized primarily to intracellular mucin droplets. Extracts of human bronchial mucin, whic h is known to contain sialic acid primarily in the SAalpha2,3Gal linka ge, was a potent inhibitor of the binding of the receptor variant stra in to trachea sections, while the binding of the parent strain was una ffected by the presence of mucin. Human bronchial mucin also inhibited the binding of the receptor variant strains, but not the parent virus strains, to human erythrocytes derivatized to contain SAalpha2,6Gal s equences. These results suggest that a combination of selection pressu res present in the respiratory tract environment have resulted in the evolution of a hemagglutinin receptor specificity in human influenza A virus strains which optimizes recognition of, binding to and infectio n of host cells.