|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1994 : ¥1,400,000 (Direct Cost : ¥1,400,000)
The receptor specificity of the HA differs amongsinfluenza viruses : most avian influenza viruses preferentially bind the sialic acid-alpha-2,3-galactose (SAalpha2-3Gal) linkage, while human influenza viruses preferentially bind the SAalpha2,6Gal linkage on cell surface sialyloligosaccharides. To understand the molecular basis of host range restriction, we examined the distribution of sialyloligosaccharides at the replication site of influenza virus in nonhuman animals. Using linkage-specific lectins, we found that epitherial cells lining duck intestine and horse trachea contain SAalpha2,3Gal but not SAalpha2,6Gal linkages, whereas those lining pig trachea contain both. We next examined why the mutant human HA,which preferentially reconizes SAalpha2,3Gal, does not support virus replication in duck intestine. The analysis of the receptor specificity of duck and mutant human viruses suggested that the recognition of N-glycolyl sialic acid (NeuGc) is iportant for intestinal replication of
virus in ducks. NeuGcalpha2,3 was immunologically detected in epitherial cells in duck uintestine. These findings show that the presence of the receptors in the replication site of animals corresponds tothe receptor specificity of viruses isolated from such animals.
To test whether agglutination of erythrocytes from different animal species could be used to assess the receptor specificity of influenza A viruses, we determined the agglutinating activities of a range of virus strains. All equine and avian viruses agglutinated erythrocytes from all of the animal ; species tested (chickens, ducks, guinea pigs, humans, sheep, forses and cows), The human viruses agglutinated all but the horse. and cow erythrocytes. Fluorescene-activated cell sorting analysis of erythrocytes using linkage-specific lectins showed that both cow and horse crythrocytes contain a large amount of SAalpha2,3Gal- but virtually no SAalpha2,6Gal-specific lectin-reactive oligosaccharides on the cell surface, while human and chicken erythrocytes contain both types of oligosaccharides. These findings show that agglutinating assays with erythrocytes from different animal species would be useful in characterizing the receptor specificity of influenza A viruses.