Summary
1 H-benz[f]indene-1.3(2H)dione-bis-amidinohydrazone (benzhydrazone) inhibited incorporation of14C-glucosamine,14C-fucose and14C-mannose into glycoproteins of HEp-2 cells infected with various strains of herpes simplex virus 1 (HSV-1) and impaired RNA and protein synthesis to a low extent. These biochemical effects are very similar to those induced by glycosylation inhibitors such as tunicamycin, D-glucosamine and 2-deoxy-D-glucose. In contrast to these inhibitors, benzhydrazone reduced HSV glycoprotein synthesis selectively since it did not significantly modify i) the saccharide uptake into glycoproteins of uninfected and of Sindbis virus-infected cells, ii) viral growth and cell fusion in paramyxovirus-infected cells, two activities which depend on viral glycoprotein synthesis. Benzhydrazone had only minor effects on the overall metabolism of uninfected cells, since it did not alter cell growth rate, and amino acid, uridine, and hexose incorporations were about 80 per cent those of untreated cells.
Similar content being viewed by others
References
Bettinger, G. E., Young, F. E.: Tunicamycin, an inhibitor of bacillus peptidoglycan synthesis: a new site of inhibition. Biochem. biophys. Res. Commun.67, 16–21 (1975).
Bosman, H. B.: Inhibition of protein, glycoprotein, ribonucleic, acid and deoxy-ribonucleic acid synthesis by D-glucosamine and other sugars in mouse leukemic cells L51784 and selective inhibition in SV-3T3 compared with 3T3 cells. Biochym. biophys. Acta240, 74–93 (1971).
Cassai, E., Manservigi, R., Corallini, A., Terni, M.: Plaque dissociation of herpes simplex viruses: biochemical and biological characters of the viral variants. Intervirology6, 212–223 (1975/76).
Cavrini, V., Gatti, R., Roveri, P., Giovanninetti, G., Mannini Palenzona, A., Baserga, M.: Antiviral compounds. XII-Synthesis andin vitro antiherpetic activity of some cyclic α- and β-diketone bis-amidinohydrazones. Eur. J. med. Chem.14, 343–346 (1979).
Choppin, P. W., Compans, R. W.: Reproduction of paramyxoviruses. In:Fraenkel-Conrat, H., Wagner, R. R. (eds.), Comprehensive Virology, Vol. 4, 95–178. New York-London: Plenum 1975.
Costanzo, F., Campadelli-Fiume, G., Foa'-Tomasi, L., Cassai, E.: Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. J. Virol.21, 996–1001 (1977).
Courtney, R. J.: Herpes simplex virus protein synthesis in the presence of 2-deoxy-D-glucose. Virology73, 286–294 (1976).
Courtney, R. J., Steiner, S. M., Benyesh-Melnick, M.: Effects of 2-deoxy-D-glucose on herpes simplex virus replication. Virology52, 447–455 (1973).
Diggelmann, H.: Biosynthesis of an unglycosylated envelope glycoprotein of Rous sarcoma virus in the presence of tunicamycin. J. Virol.30, 799–804 (1979).
Duda, V. E., Schlesinger, M. J.: Alterations in Sindbis viral envelope proteins by treating BHK cells with glucosamine. J. Virol.15, 416–419 (1975).
Ejercito, P. L., Kieff, E. D., Roizman, B.: Characterization of herpes simplex strains differing in their effects on social behaviour of infected cells. J. gen. Virol.2, 357–364 (1968).
Heine, J. W., Honess, R. W., Cassai, E., Roizman, B.: Proteins specified by herpes simplex virus. XII. The virion polypeptides of type 1 strains. J. Virol.14, 640–651 (1974).
Hoggan, M. D., Roizman, B.: The isolation and properties of a variant of herpes simplex producing multinucleated giant cells in monolayer cultures in the presence of antibody. Amer. J. Hygiene70, 208–209 (1959).
Honess, R. W., Roizman, B.: Proteins specified by herpes simplex virus. XIII. Glycosylation of viral polypeptides. J. Virol.16, 1308–1326 (1975).
Horio, D. T., Spear, P. G.: Effects of tunicamycin on the structure and function of envelope glycoproteins specified by herpes simplex virus (HSV). Abstracts of the annual meeting of the American Society for Microbiology, p. 309, Los Angeles, 1979.
Kaluza, G., Scholtissek, C., Rott, R.: Inhibition of the multiplication of enveloped RNA viruses by glucosamine and 2-deoxy-D-glucose. J. gen. Virol.14, 251–259 (1972).
Keller, J. M., Spear, P. G., Roizman, B.: Proteins specified by herpes simplex virus. III. Viruses differing in their effects on the social behavior on infected cells specify different membrane glycoproteins. Proc. Nat. Acad. Sci. U.S.A.65, 865 to 871 (1970).
Klenk, H. D., Scholtissek, C., Rott, R.: Inhibition of glycoprotein biosynthesis of influenza virus by D-glucosamine and 2-deoxy-D-glucose. Virology49, 723–734 (1972).
Knowles, R. W., Person, S.: Effects of 2-deoxyglucose, glucosamine and mannose on cell fusion and the glycoproteins of herpes simplex virus. J. Virol.18, 644–651 (1976).
Kuo, S. C., Lampen, J. O.: Tunicamycin: an inhibitor of yeast glycoprotein synthesis. Biochem. biophys. Res. Commun.58, 287–295 (1974).
Leavitt, R., Schlesinger, S., Kornfeld, S.: Tunicamycin inhibits glycosylation and multiplication of Sindbis and vesicular stomatitis viruses. J. Virol.21, 375–385 (1977).
Lewandowsky, L. J., Smith, R. E., Bolognesi, D. P., Halpern, M. S.: Viral glycoprotein synthesis under conditions of glucosamine block in cells transformed by avian sarcoma viruses. Virology66, 347–355 (1975).
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. biol. Chem.193, 265–275 (1951).
Manservigi, R., Spear, P. G., Buchan, A.: Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. Proc. Nat. Acad. Sci. U.S.A.74, 3913–3917 (1977).
Olofsson, S., Khanna, B, Lycke, E: Altered kinetic properties of sialyl and galactosyl transferases associated with Herpes simplex virus infection of GMK and BHK cells. J. gen. Virol.47, 1–9 (1980).
Roizman, B.: Herpesviruses, membranes and the social behavior of infected cells. In:Sanders, M. (ed.), Viruses affecting man and animals, 37–71. St. Louis, Mo.: Green 1970.
Sarmiento, M., Haffey, M., Spear, P. G.: Membrane proteins specified by herpes simplex virus. III. Role of glycoprotein VP7 (B2) in virion infectivity. J. Virol.29, 1149–1158 (1979).
Scheid, A., Choppin, P. W.: Identification and biological activities of paramyxoviruses glycoproteins. Activation of cell fusion hemolysis and infectivity by proteolytic cleavage of an inactive precursor protein of Sendai virus. Virology57, 475–490 (1974).
Scheid, A., Choppin, P. W.: Isolation of paramyxovirus glycorpoteins and identification of their biological properties. In:Mahy, B. W. J., Barry, R. D. (eds.), Negative strand viruses, 177–192. London: Academic Press 1975.
Schlesinger, S., Schlesinger, M. J.: Formation of Sindbis virus proteins: identification of a precursor for one of the envelope proteins. J. Virol.10, 925–932 (1972).
Scholtissek, C.: Inhibition of the multiplication of enveloped viruses by glucose derivatives. Curr. Top. Microbiol. Immunol.70, 101–119 (1975).
Schwarz, R. T., Klenk, H. D.: Inhibition of glycosylation of the influenza virus hemagglutinin. J. Virol.14, 1023–1034 (1974).
Schwarz, R. T., Rohrschneider, J. M., Schmidt, M. F. G.: Suppression of glycoprotein formation of semliki forest, influenza, and avian sarcoma virus by tunicamycin. J. Virol.19, 782–791 (1976).
Spear, P. G.: Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells. J. Virol.17, 991–1008 (1976).
Takatsuki, A., Tamura, G.: Effect of tunicamycin on the synthesis of macromolecules in cultures of chick embryo fibroblasts infected with Newcastle disease virus. J. Antibiot.24, 785–794 (1971).
Tkacz, J. S., Lampen, J. O.: Tunicamycin inhibition of polyisoprenil N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomes. Biochem. biophys. Res. Commun.65, 248–257 (1975).
Author information
Authors and Affiliations
Additional information
With 6 Figures
Rights and permissions
About this article
Cite this article
Campadelli-Fiume, G., Sinibaldi-Vallebona, P., Cavrini, V. et al. Selective inhibition of herpes simplex virus glycoprotein synthesis by a benz-amidinohydrazone derivative. Archives of Virology 66, 179–191 (1980). https://doi.org/10.1007/BF01314732
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01314732