AVIAN INFLUENZA-A VIRUSES DIFFER FROM HUMAN VIRUSES BY RECOGNITION OFSIALYLOLIGOSACCHARIDES AND GANGLIOSIDES AND BY A HIGHER CONSERVATION OF THE HA RECEPTOR-BINDING SITE

Avian influenza virus strains representing most hemagglutinin (HA) sub types were compared with human influenza A (H1N1, H3N2) and B virus is olates, including those with no history of passaging in embryonated he n's eggs, for their ability to bind free N-acetylneuraminic acid (Neu5 Ac) and sialyloligosaccharides in a competitive binding assay and to a ttach to gangliosides in a solid-phase adsorption assay. The avian vir uses, irrespective of their HA subtype, showed a higher affinity for s ialyl-3-lactose and the other Neu5Ac2-3Gal-terminated oligosaccharides and a lower affinity for sialyl-6-lactose than for free Neu5Ac, indic ative of specific interactions between the HA and the 3-linked Gal and poor accommodation of 6-linked Gal in the avian receptor-binding site (RES). Human H1 and H3 strains, by contrast, were unable to bind to 3 -linked Gal, interacting instead with the asialic portion of sialyl-6- (N-acetyllactosamine). Different parts of this moiety were recognized by H3 and H1 subtype viruses (Gal and GlcNAc, respectively). Compariso n of the HA amino acid sequences revealed that residues in positions 1 38, 190, 194, 225, 226, and 228 are conserved in the avian RBS, while the human HAs harbor substitutions at these positions. A characteristi c feature of avian viruses was their binding to Neu5Ac2-3Gal-containin g gangliosides. This property of avian precursor viruses was preserved in early human H3 isolates, but was gradually lost with further circu lation of the H3 HA in humans. Consequently, later human H3 isolates, as well as H1 and type B human strains, were unable to bind to short N eu5Ac2-3Gal-terminated gangliosides, an incompatibility that correlate d with higher glycosylation of the HA globular head of human viruses. Our results suggest that the RES is highly conserved among HA subtypes of avian influenza virus, while that of human viruses displays distin ctive genotypic and phenotypic variability. (C) 1997 Academic Press.