Design of Virus-Specific Inhibitors of Terminal Glycosylation Enhancing the Antigenicity of Viral Glycoproteins

  • R. Datema
  • S. Olofsson
Conference paper

Abstract

The studies described here show three findings essential for the design of inhibitors of terminal glycosylation selective for virus-infected cells: (1) terminal glycosyl residues can modulate the antigenicity of viral glycoproteins, for example by masking potential neutralizing epitopes; (2) inhibition of translocation of sugar nucleotides into the Golgi-lumen can lead to interference with terminal glycosylation (branching; galactose addition, sialic acid addition) giving rise to increased antigenicity of viral glycoproteins; (3) terminal glycosylation inhibitors can be generated in virus-infected cells by virus-coded enzymes. Design of inhibitors based on these findings may complement antiviral therapy and increase our understanding of the role of terminal glycosylation of viral glycoproteins in the intact host.

Keywords

Influenza Oligosaccharide Galactose Pyrimidine Nucleoside 

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References

  1. 1.
    Kornfeld R and Kornfeld S, Assembly of asparagine-linked oligosaccharides. Annu. Rev. Biochem. 54: 631–664, 1985.PubMedCrossRefGoogle Scholar
  2. 2.
    Datema R, Olofsson S and Romero PA, Inhibitors of protein glycosylation and glycoprotein processing in viral systems. Pharmac. Ther. 33: 221–286, 1987.CrossRefGoogle Scholar
  3. 3.
    Schachter H, Coordination between enzyme specificity and intracellular compartmentation in the control of protein-bound oligosaccharide biosynthesis. Biochem. Cell Biol. 64: 163–181, 1986.PubMedCrossRefGoogle Scholar
  4. 4.
    Schwarz RT and Datema R, The lipid pathway of protein glycosylation and its inhibitors: the biological significance of protein-bound carbohydrates. Adv. Carbohydr. Chem. Biochem. 40: 287–379, 1982.PubMedCrossRefGoogle Scholar
  5. 5.
    Elbein AD, Inhibitors of the biosynthesis and processing of N-linked oligosaccharides. Crit. Rev. Biochem. 16: 21–49, 1984.CrossRefGoogle Scholar
  6. 6.
    Schwarz RT and Datema R, Inhibitors of protein glycosylation. Trends Biochem. Sci. 5: 65–67, 1980.CrossRefGoogle Scholar
  7. 7.
    Schwarz RT and Datema R, Inhibitors of trimming: new tools in glycoprotein research. Trends Biochem. Sci. 9: 32–34, 1984.CrossRefGoogle Scholar
  8. 8.
    Romero PA, Saunier B and Herscovics A, Comparison between 1-deoxynojirimycin and Nmethyl-l-deoxynojirimycin as inhibitors of oligosaccharide processing in intestinal epithelial cells. Biochem. J. 226: 733–740, 1985.PubMedGoogle Scholar
  9. 9.
    Pan YT, Hon H, Saul R, Sanford BA, Molyneux RJ and Elbein AD, Castanosperimine inhibits the processing of the oligosaccharide portion of the influenza viral hemagglutinin. Biochemistry 22: 3975–3984, 1983.PubMedCrossRefGoogle Scholar
  10. 10.
    Kino T, Inamura N, Nakahara K, Kiyoto S, Goto Y, Terano H, Koshaka M, Aoki H and Imanaka H, Studies of an immunomodulator, swainsonine. II. Effect of swainsonine on mouse immunodeficient system and experimental murine tumor. J. Antibiot. 38: 936–939, 1989.CrossRefGoogle Scholar
  11. 11.
    Humphries MJ, Matsumoto K, White SL and Olden K, Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16–F10 murine melanoma cells. Proc. Natl. Acad. Sci. 83: 1752–1756, 1986.PubMedCrossRefGoogle Scholar
  12. 12.
    Dennis JW, Laferté S, Waghome C, Bretman ML and Kerbel RS, ß(1–6)Branching of Asn-linked oligosaccharides is directly associated with metastasis. Science 236: 582–585, 1987.PubMedCrossRefGoogle Scholar
  13. 13.
    Montefiori DC, Robinson E and Mitchell WM, Antibody-independent, complement-mediated enhancement of HIV-1 infection by mannosidase I and H inhibitors. Antiviral Res. 11: 137–146, 1989.PubMedCrossRefGoogle Scholar
  14. 14.
    Sjöblom I, Lundström M, Sjögren-Jansson E, Glorioso JC, Jeansson S and Olofsson S, Demonstration and mapping of highly carbohydrate-dependent epitopes in the herpes simplex virus type 1-specified glycoprotein C. J. Gen.Virol. 68: 545–554, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Olofsson S, Sjöblom I and Jeansson S, Activity of herpes simplex virus type 1-specified glycoprotein C antigenic site II epitopes reversibly modulated by peripheral fucose or galactose units of glycoprotein oligosaccharides. J. Gen.Virol 71: 889–895, 1990.PubMedCrossRefGoogle Scholar
  16. 16.
    Huso DL, Narayan O and Hart GW, Sialic acids on the surface of caprine arthritis encephalitis virus define the biological properties of the virus. J. Virol. 62: 1974–1980, 1988.PubMedGoogle Scholar
  17. 17.
    Feizi I and Childs RA, Carbohydrate structures of glycoproteins and glycolipids as differentiation antigens, tumor associated antigens and components of receptor systems. Trends Biochem. Sci. 10: 24–27, 1985.CrossRefGoogle Scholar
  18. 18.
    Hirschberg CB and Snider MD, Topography of glycosylation in the rough endoplasmic reticulum and Golgi apparatus. Annu. Rev. Biochem. 56: 63–88, 1987.PubMedCrossRefGoogle Scholar
  19. 19.
    Datema R and Olofsson S, Nucleotide analogs as herpesvirus-specific inhibitors of protein glycosylation. In: Nucleotide Analogs as Antiviral Agents (Martin JC ed.); American Chemical Society, pp. 116–123, 1989.Google Scholar
  20. 20.
    Capasso JM and Hirschberg CB, Effect of nucleotides on translocation of sugar nucleotides and adenosine 3’-phosphate 5’-phosphosulfate into Golgi apparatus vesicles. Biochim. Biophys. Acta 777: 133–239, 1984.PubMedCrossRefGoogle Scholar
  21. 21.
    DeClercq E, Specific targets for antiviral drugs. Biochem. J. 205: 1–13, 1982.Google Scholar
  22. 22.
    Olofsson S, Milla M, Hirschberg C, DeClercq E and Datema R, Inhibition of terminal N-and O-glycosylation specific for herpesvirus-infected cells. Mechanism of an inhibitor of sugar nucleotide transport across Golgi membranes. Virology 166: 440–150, 1988.PubMedCrossRefGoogle Scholar
  23. 23.
    Olofsson S, Lundström M and Datema R, The antiherpes drug (E)-5-(2-bromovinyl)-2’deoxyuridine (BVdU) interferes with formation of N-linked and 0-linked oligosaccharides of the herpes simplex virus type 1 glycoprotein C. Virology 147: 201–205, 1985.PubMedCrossRefGoogle Scholar
  24. 24.
    Montreuil J, Structure and conformation of glycoprotein glycans. In: Vertebrate Lectins (Olden K and Parent JB eds), Van Nostrand; pp. 1–26, 1987.Google Scholar
  25. 25.
    Rademacher TW, Parekh RB and Dwek RA, Glycobiology. Annu. Rev. Biochem. 57: 785–838, 1988.PubMedCrossRefGoogle Scholar
  26. 26.
    Marlin SD, Holland TC, Levine M and Glorioso JC, Epitopes of herpes simplex type 1 glycoprotein gC are clustered in two distinct antigenic sites. J. Virol. 53: 128–136, 1989.Google Scholar
  27. 27.
    Olofsson S and Datema R, New virus-selective inhibitor of terminal glycosylation increasing immunological reactivity of a viral glycoprotein. Antivir. Chem. Chemother. 1: 17–24, 1990.Google Scholar
  28. 28.
    Olofsson S, Sjöblom I, Glorioso JC, Jeansson S and Datema R, Selective induction of discrete epitopes of herpes simplex virus type 1-specified glycoprotein C by interference with terminal steps in glycosylation. J. Gen. Virol. 72: 1959–1966, 1991.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • R. Datema
    • 1
  • S. Olofsson
    • 2
  1. 1.Department of Antiretroviral TherapySandoz Research Institute ViennaViennaAustria
  2. 2.Department of Clinical VirologyUniversity of GöteborgGöteborgSweden

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