title: Interplay between carbohydrate in the stalk and the length of the connecting peptide determines the cleavability of influenza virus hemagglutinin.
abstract: The ability of many viruses to replicate in host cells depends on cleavage of certain viral glycoproteins, including hemagglutinin (HA). By generating site-specific mutant HAs of two highly virulent influenza viruses, we established that the relationship between carbohydrate in the stalk and the length of the connecting peptide is a critical determinant of cleavability. HAs that lacked an oligosaccharide side chain in the stalk were cleaved regardless of the number of basic amino acids at the cleavage site, whereas those with the oligosaccharide side chain resisted cleavage unless additional basic amino acids were inserted. This finding suggests that the oligosaccharide side chain interferes with HA cleavage if the number of basic amino acids at the cleavage site is not adequate to nullify this effect. Similar interplay could influence cleavage of other viral glycoproteins, such as those of human and simian immunodeficiency viruses and paramyxoviruses.
authors.affiliation: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: R G
authors.initials: RG
authors.lastname: Webster
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D050260:Carbohydrate Metabolism; D006031:Glycosylation; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism*; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009844:Oligosaccharides / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D006389:Hemagglutinins, Viral; D009844:Oligosaccharides