Host cell- and virus strain-dependent differences in oligosaccharides of hemagglutinin glycoproteins of influenza A viruses

Abstract

The effect of the host cell and virus strain on the glycosylation of influenza A virus hemagglutinin glycoproteins was investigated by analysis of Pronase-digested glycopeptides labeled with radioactive sugar precursors. When influenza A/WSN virus was grown in MDBK cells, HA 1 contained both complex galactose-containing (type I) and mannose-rich (type II) glycopeptides, but HA 2 lacked type II glycopeptides. In contrast, type I and type II glycopeptides were found in HA 1 as well as HA 2 isolated from virus grown in primary chick embryo fibroblast cells, indicating that whether type I or type II oligosaccharide chains are attached to HA polypeptides is determined in part by the host cell type. However, analyses of glycopeptides from various influenza A strains representative of all human antigenic subtypes grown in a single host cell type, MDCK cells, revealed that the oligosaccharide types associated with HA polypeptides also depend on the virus strain. Both type I and type II glycopeptides were found in all strains tested, and there was no significant difference in the sizes of these glycopeptides among the strains. However, strain-dependent differences were observed in the relative amounts of type I and type II glycopeptides in virions as well as isolated glycoproteins HA 1 or HA 2. Such differences were evident among influenza A strains of the same as well as distinct HA subtypes, which suggests that changes in primary structure of the HA polypeptides induced by either antigenic drift or major antigenic shifts have caused the variation in oligosaccharide chains associated with these polypeptides.