title: Elongation of the N-acyl side chain of sialic acids in MDCK II cells inhibits influenza A virus infection.
abstract: The interaction of influenza A virus with sialyated receptor components is one of the best characterized ligand-receptor interactions. We pretreated MDCK II host cells with three different N-acyl-modified sialic acid precursor analogues, N-propanoyl, N-butanoyl or N-pentanoyl D-mannnosamine. Cellular sialic acid biosynthesis yielded 18-35% of new, modified sialic acids on cell surface glycoconjugates, N-propanoyl, N-butanoyl or N-pentanoyl neuraminic acid, respectively. The elongation of the N-acyl group of sialic acids resulted in an inhibition of influenza A virus (strain X31) binding and subsequent infection of up to 80%. In contrast, the sialic acid-independent infection of vesicular stomatitis virus was unaffected in these cells. Molecular modeling studies based on the crystal structure of the influenza A virus hemagglutinin complexed with sialyllactose suggest a steric hindrance of hemagglutinin binding to aliphatically elongated N-acyl groups. We propose that biosynthetic sialic acid modification in conjunction with molecular modeling is a potent tool to further analyze the influenza A virus-receptor interaction.
authors.affiliation: Angewandte Tumorvirologie, Zentrale Spektroskopie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: O T
authors.initials: OT
authors.lastname: Keppler
authors.forename: M
authors.initials: M
authors.lastname: Herrmann
authors.forename: C W
authors.initials: CW
authors.lastname: von der Lieth
authors.forename: P
authors.initials: P
authors.lastname: Stehling
authors.forename: W
authors.initials: W
authors.lastname: Reutter
authors.forename: M
authors.initials: M
authors.lastname: Pawlita
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000502:physiology*; D002236:Carbohydrate Conformation; D002460:Cell Line; D004285:Dogs; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006595:Hexosamines / Q000494:pharmacology; D009980:Influenza A virus / Q000254:growth & development* / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008958:Models, Molecular; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D006389:Hemagglutinins, Viral; D006595:Hexosamines; C116505:N-butanoylmannosamine; C116506:N-pantanoylmannosamine; D011991:Receptors, Virus; C076271:N-propanoylmannosamine; D019158:N-Acetylneuraminic Acid