Specificity of the N1 and N2 sialidase subtypes of human influenza A virus for natural and synthetic gangliosides

Abstract

Sialyl-linkage specificity of sialidases of the human influenza A virus strains, A/Aichi/2/68 (H3N2) and A/PR/8/34 (H1N1) were studied using natural and synthetic gangliosides. The sialidase of the A/Aichi/2/68 strain hydrolyzed the terminal Neu5Acα2-3Gal sequence but not the Neu5Acα2-3 linkage on the inner Gal of GM1a, which is a ganglioside that has the gangliotetraose chain (Galβ1-3GalNAcβ1-4-(Neu5Acα2-3) Galβ1-4Glcβ1- Cer). The sialidase hydrolyzed the Neu5Ac on the inner Gal of GM2, which had a shorter gangliotriose chain. GM4, which had the shortest chain (Neu5Acα2- 3Galβ1-Cer) of the gangliosides, had a lower substrate specificity. The N1 and N2 sialidase subtypes of the human influenza A virus had no significant variation in their substrate specificity for the gangliosides. Analysis of 11 synthetic gangliosides, which contained various ceramide or sialic acid moieties, demonstrated that A/Aichi/2/68 (H3N2) sialidase recognized the ceramide and sialic acid moiety and the length and structure of the sialyl sugar chain.