BIOSYNTHETIC MODULATION OF SIALIC ACID-DEPENDENT VIRUS-RECEPTOR INTERACTIONS OF 2 PRIMATE POLYOMA VIRUSES

Sialic acids are essential components of the cell surface receptors of many microorganisms including viruses, A synthetic, N-substituted D-m annosamine derivative has been shown to act as precursor for structura lly altered sialic acid incorporated into glycoconjugates in vivo (Kay ser, H., Zeitler, R., Kannicht, C., Grunow, D., Nuck, R., and Reutter, W. (1992) J. Biol. Chem. 267, 16934-16938). In this study we have ana lyzed the potential of three different sialic acid precursor analogues to modulate sialic acid-dependent virus receptor function on differen t cells, We show that treatment with these D-mannosamine derivatives c an result in the structural modification of about 50% of total cellula r sialic acid content, Treatment interfered drastically and specifical ly with sialic acid-dependent infection of two distinct primate polyom a viruses, Both inhibition (over 95%) and enhancement (up to 7-fold) o f virus binding and infection were observed depending on the N-acyl su bstitution at the C-5 position of sialic acid, These effects were attr ibuted to the synthesis of metabolically modified, sialylated virus re ceptors, carrying elongated N-acyl groups, with altered binding affini ties for virus particles, Thus, the principle of biosynthetic modifica tion of sialic acid by application of appropriate sialic acid precurso rs to tissue culture or in vivo offers new means to specifically influ ence sialic acid-dependent ligand-receptor interactions and could be a potent tool to further clarify the biological functions of sialic aci d, in particular its N-acyl side chain.