Summary
In herpes simplex virus-infected (HSV) cells, the antiviral nucleoside analogue 5-n-propyl-2′-deoxyuridine (PdU) may, under certain circumstances, induce a pattern of interference with late steps in formation of N-linked glycans, resulting in increased availability of viral glycoproteins for neutralizing antibodies. The PdU-induced changes in N-linked glycans, released by pronase digestion of the HSV-specified glycoprotein gC-1, were investigated by using lectin affinity chromatography and Bio-Gel P6 gel filtration of glycans, radiolabelled with [3H]galactose or [3H]glucosamine. PdU-treatment of HSV-infected cells totally inhibited addition of sialic acid and reduced the amount of galactose incorporated into N-linked glycans by 70%. In addition, the PDU-treatment caused a decrease in oligosaccharides with affinity forPhaseoulus vulgaris leuco-agglutinin and erythro-agglutinin, and an increase inLens culinaris lectin (LCA)-binding oligosaccharides, suggesting a PdU-induced shift from multi-branched to moderately branched structures. This shift was also found in HSV-infected B16 mouse melanoma cells, where the large content of multi-branched oligosaccharides contributes to the metastatic potential. The LCA-binding glycans from PdU-treated cells were smaller and contained less galactose units than corresponding structures from untreated cells. In a cell-free system, PdU 5′-monophosphate inhibited the translocation of UDP-GlcNAc, and, to a smaller extent, also the translocation of UDP-galactose into Golgi vesicles, suggesting that nucleotide sugar translocation is one important target for the PdU-induced interference with glycosylation in HSV-infected cells.
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References
Alexander S, Elder JH (1984) Carbohydrate dramatically influences immune reactivity of antisera to viral glycoprotein antigens. Science 226: 1328–1330
Campadelli-Fiume G, Sinibaldi-Vallebona P, Cavrini V, Mannini-Palenzona A (1980) Selective inhibition of herpes simplex virus glycoprotein synthesis by a benz-amidinohydrazone derivative. Arch Virol 66: 179–191
Cummings RD, Kornfeld S (1982) Fractionation of asparagine-linked oligosaccharides by serial lectin-agarose affinity chromatography. A rapid, sensitive technique. J Biol Chem 257: 11235–11240
Datema R, Olofsson S, Romero P (1987) Inhibitors of protein glycosylation and glycoprotein processing in viral systems. Pharmacol Ther 33: 221–286
De Clercq E, Walker RT (1984) Synthesis and antiviral properties of 5-vinylpyrimidine analogs. Pharmacol Ther 26: 1–44
Dennis JW, Laferté S, Waghorne C, Breitman ML, Kerbel RS (1987) β1–6 Branching of Asn-linked oligosaccharides is directly associated with metastasis. Science 236: 582–585
Elbein AD, Solf R, Dorling PR, Vosbeck K (1981) Swainsonine: an inhibitor of glycoprotein processing. Proc Natl Acad Sci USA 78: 7393–7397
Giziewicz L, Shugar D (1978) Nucleotide 5′-phosphates. Enzymatic phosphorylation of nucleosides of the 5′-phosphates. In: Townsend LB, Tipson RS (eds) Nucleic acid chemistry, part 2. Wiley, New York, pp 955–961
Green ED, Baenziger JU (1987) Oligosaccharide specificities ofPhaseolus vulgaris leukoagglutinating and erythroagglutinating phytohemagglutinins. Interactions with N-glycanase-released oligosaccharides. J Biol Chem 262: 12018–12029
Günalp A (1965) Growth and cytopathic effect of rubella virus in a line of green monkey kidney cells. Proc Soc Exp Biol Med 118: 85–90
Hellstrand K, Asea A, Hermodsson S (1990) Role of histamine in natural killer cell-mediated resistance against tumor cells. J Immunol 145: 4365–4370
Humphries MJ, Matsumoto K, White SL, Olden K (1986) Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells. Proc Natl Acad Sci USA 83: 1752–1756
Kornfeld K, Reitman ML, Kornfeld R (1981) The carbohydrate-binding specificity of pea and lentil lectins. Fucose is an important determinant. J Biol Chem 256: 6633–6640
Kulikowski T, Zawadzki Z, De Clercq E, Shugar D (1984) 5-Substituted arabinofur-anosyluracil nucleosides. Synthesis and antiviral properties. Acta Biochim Polon 31: 341–356
Leelavetti DE, Estes LW, Feingold DS, Lombardi B (1970) Isolation of a Golgi-rich fraction from rat liver. Biochim Biophys Acta 211: 124–138
Mancini WR, De Clercq E, Prusoff WH (1983) The relationship between incorporation of (E)-5-(2-bromovinyl)-2′-deoxyuridine into herpes simplex virus type 1 DNA with virus infectivity and DNA integrity. J Biol Chem 258: 792–795
Olofsson S, Sjöblom I, Lundström M, Jeansson S, Lycke E (1983) Glycoprotein C of herpes simplex virus: characterization of O-linked oligosaccharides. J Gen Virol 64: 2735–2747
Olofsson S, Lundström M, Datema R (1985) The antiherpes drug (E)-5-(2-bromovinyl)2′-deoxyuridine (BVdU) interferes with the formation of N-linked and O-linked oligosaccharides of the herpes simplex virus type 1 glycoprotein C. Virology 147: 201–205
Olofsson S, Milla M, Hirschberg C, De Clercq E, Datema R (1988) Inhibition of terminal N- and O-glycosylation specific for herpesvirus-infected cells. Mechanism of an inhibitor of sugar nucleotide transport across the Golgi membrane. Virology 166: 440–450
Olofsson S, Datema R (1990) New virus-selective inhibitor of terminal glycosylation increasing immunological reactivity of a viral glycoprotein. Antiviral Chem Chemother 1: 17–24
Olofsson S, Sjöblom I, Jeansson S (1990) Activity of herpes simplex virus type 1-specified glycoprotein C antigenic site II epitopes modulated by peripheral fucose or galactose units of glycoprotein oligosaccharides. J Gen Virol 71: 889–895
Olofsson S, Sjöblom I, Glorioso JC, Jeansson S, Datema R (1991) Selective induction of discrete epitopes of herpes simplex virus specified glycoprotein C by interference with terminal steps in glycosylation. J Gen Virol 72: 1959–1966
Paquett MR, Narasimhan S, Schachter H, Moscarello MA (1984) Branch specificity of purified rat liver Golgi UDP-galactose: nacetylglucosamine β1,4-galactosyl transferase. Preferential transfer of galactose on the GlcNAc β1,2-Man 1,3-branch of a complex biantennary Asn-linked oligosaccharide. J Biol Chem 259: 4716–4721
Perez M, Hirschberg CB (1987) Transport of sugar nucleotides into the lumen of vesicles derived from the rough endoplasmic reticulum and Golgi apparatus. In: Colowich SP, Kaplan NO (eds) Methods in enzymology, vol 138. Academic Press, New York, pp 709–715
Ruth JL, Cheng Y (1982) Selective antiviral agents. The metabolism of 5-propyl-2′-deoxyuridine and effects of DNA synthesis in herpes simplex virus type 1 infections. J Biol Chem 257: 10263–10266
Schachter H (1986) Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosaccharides. Biochem Cell Biol 64: 163–181
Serafini-Cessi F, Campadelli-Fiume G (1981) Studies of benzhydrazone, a specific inhibitor of herpesvirus glycoprotein synthesis. Size distribution of glycopeptides, and endo-N-acetylglucosaminidase-H treatment. Arch Virol 70: 331–341
Sjöblom I, Lundström M, Sjögren-Jansson E, Glorioso JC, Jeansson S, Olofsson S (1987) Demonstration and mapping of highly carbohydrate-dependent epitopes in the herpes simples virus type 1-specified glycoprotein C. J Gen Virol 68: 545–554
Swierkowski M, Shugar D (1969) A non-mutagenic thymidine analog with antiviral activity. 5-Ethyldeoxyuridine. J Med Chem 12: 533–534
Tulsiani DRP, Harris TM, Touster O (1983) Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II. J Biol Chem 258: 7578–7585
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Olofsson, S., Sjöblom, I., Hellstrand, K. et al. 5-Propyl-2-deoxyuridine induced interference with glycosylation in herpes simplex virus infected cells. Archives of Virology 128, 241–256 (1993). https://doi.org/10.1007/BF01309437
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DOI: https://doi.org/10.1007/BF01309437