Elongation of the N-acyl side chain of sialic acids in MDCK II cells inhibits influenza A virus infection.

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.