Ligand recognition by influenza virus. The binding of bivalent sialosides

• Published in: The Journal of biological chemistry 1991-12, Vol.266 (35), p.23660-23669
• Main Authors: GLICK, G. D, TOOGOOD, P. L, WILEY, D. C, SKEHEL, J. J, KNOWLES, J. R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carbohydrate Conformation; Carbohydrate Sequence; cell adhesion; Chickens; Erythrocytes - physiology; Fundamental and applied biological sciences. Psychology; Hemagglutination; hemagglutinin; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral - physiology; Ligands; Light; Magnetic Resonance Spectroscopy; Microbiology; Molecular Sequence Data; Molecular Structure; Orthomyxoviridae - physiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Scattering, Radiation; Sialic Acids - chemical synthesis; Sialic Acids - metabolism; sialosides; Virology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)54335-0

Infection by influenza virus is initiated by a cellular adhesion event that is mediated by the viral protein, hemagglutinin, which is exposed on the surface of the virion. Hemagglutinin recognizes and binds to cell surface sialic acid residues. Although each individual ligand binding interaction is weak, the high affinity of influenza virus for cells that bear sialic acid residues is thought to result from a multivalent attachment process involving many similar recognition events. To evaluate such binding we have synthesized three series of compounds, each containing two sialic acid residues separated by spacers of different length, and have tested them as ligands for influenza hemagglutinin. No increased binding to the bromelain-released hemagglutinin ectodomain was seen for any of the bivalent compounds as determined by 1H NMR titration. In contrast, however, a spacer length between sialic acid residues of approximately 55 A sharply increases the binding of these bidentate species to whole virus as determined by hemagglutination inhibition assays. The most effective compound containing glycines in the linking chain displayed 100-fold increased affinity for whole virus over the paradigm monovalent ligand, Neu5Ac alpha 2Me.