Recognition of monovalent sialosides by influenza virus H3 hemagglutinin.
This report presents a procedure for evaluating the relative affinities of simple sialoside receptor determinants for their interaction with the receptor binding pocket of the influenza virus hemagglutinin. The virus examined was A/Memphis/102/72, previously shown to exhibit preferential binding specificity for enzymatically modified erythrocytes containing the NeuAc alpha 2,6Gal linkage. Sialosides examined included those with structures representative of terminal sequences found on carbohydrate groups of naturally occurring glycoproteins and glycolipids. Sialosides with the NeuAc alpha 2,6Gal and NeuAc alpha 2,6GlcNAc linkage were 5-30 times more potent inhibitors than those with the NeuAc alpha 2,3Gal linkage. The results provide evidence that the previously reported specificity of the A/Memphis/102/72 hemagglutinin for the NeuAc alpha 2,6Gal sequence on cell surface receptors was due to differential affinity of the receptor binding pocket for sialoside sequences, apart from contributions due to the protein or lipid portions of the cell surface receptors. A number of synthetic sialic acid glycosides were also evaluated as inhibitors of viral attachment. The differential inhibition observed with these receptor analogs may provide clues to the detailed molecular interaction of sialosides with the hemagglutinin binding pocket and aid in the design of small molecular weight inhibitors of viral adsorption to cells.
Pritchett
T J
TJ
Department of Biological Chemistry, UCLA School of Medicine 90024.
Brossmer
R
R
Rose
U
U
Paulson
J C
JC
D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006001:Glycoconjugates / Q000378:metabolism; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D009980:Influenza A virus / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006001:Glycoconjugates; D006389:Hemagglutinins, Viral; D011991:Receptors, Virus; D012794:Sialic Acids