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. 1987;94(3):229–245. doi: 10.1007/BF01310716

Inhibition by monensin of human cytomegalovirus DNA replication

C J Kaiser 1, K Radsak 1
PMCID: PMC7086728  PMID: 3034210

Summary

Monensin, at concentrations which depended on the multiplicity of infection, was found to prevent DNA replication of human cytomegalovirus (HCMV) as well as production of viral progeny in human foreskin fibroblasts. The drug did not affect DNA replication of herpes simplex virus. Inhibition of consecutive HCMV DNA synthesis was also observed following delayed addition of the drug within 12–24 hours postinfection, but was fully reversible upon its removal. Viral replication proceeded, however, without impairment in cultures treated with monensin prior to infection. Induction of viral DNA polymerase activity was not impeded by the inhibitor. Analysis of protein- and glycoprotein synthesis revealed that monensin interfered with the production of a number of HCMV-specific polypeptides. Furthermore, evidence was obtained that the drug may hinder intracellular transport of a 135 kd glycopolypeptide.

Keywords: Infectious Disease, Polypeptide, Herpes Simplex, Viral Replication, Polymerase Activity

Footnotes

With 6 Figures

References

  • 1.Bonner WM, Laskey RA. A film detection method for tritium-labeled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974;46:83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  • 2.Britt WJ, Auger D. Synthesis and processing of the envelope gp 55–116 complex of human cytomegalovirus. J Virol. 1986;58:185–191. doi: 10.1128/jvi.58.1.185-191.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Demarchi J, Kaplan AS. Physiological state of embryonic human lung cells affect their response to human cytomegalovirus. J Virol. 1977;23:126–132. doi: 10.1128/jvi.23.1.126-132.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Fioretti A, Furukawa T, Santoli D, Plotkin S. Nonproductive infection of guinea pig cells with human cytomegalovirus. J Virol. 1973;11:998–1003. doi: 10.1128/jvi.11.6.998-1003.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Furukawa T, Fioretti A, Plotkin S. Growth characteristics of cytomegalovirus in human fibroblasts with the demonstration of protein synthesis early in viral replication. J Virol. 1973;11:991–997. doi: 10.1128/jvi.11.6.991-997.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Furukawa T, Gönczöl E, Starr S, Tolpin MD, Arbeter A, Plotkin S. HCMV envelope antigens induce both humoral and cellular immunity in guinea pig. Proc Soc Exp Biol Med. 1984;175:243–250. doi: 10.3181/00379727-175-41796. [DOI] [PubMed] [Google Scholar]
  • 7.Furukawa T, Tanaka S, Plotkin S. Restricted growth of human cytomegalovirus in UV-irradiated WI-38 human fibroblasts. Proc Soc Exp Biol Med. 1975;148:1249–1251. doi: 10.3181/00379727-148-38726. [DOI] [PubMed] [Google Scholar]
  • 8.Gallwitz D, Bos E, Stahl H. Translation of HeLa cell histone messenger RNA in cell-free protein synthesizing systems from rabbit reticulocytes, HeLa cells and wheat germ. Methods Cell Biol. 1978;19:197–213. doi: 10.1016/s0091-679x(08)60025-4. [DOI] [PubMed] [Google Scholar]
  • 9.Giles KW, Myers A. An improved diphenylamine method for the estimation of deoxyribonucleic acid. Nature. 1965;206:93. [Google Scholar]
  • 10.Hirai K, Watanabe Y. Induction of alpha-type DNA polymerases in human cytomegalovirus-infected Wi-38 cells. Biochim Biophys Acta. 1976;447:328–339. doi: 10.1016/0005-2787(76)90056-3. [DOI] [PubMed] [Google Scholar]
  • 11.Iwasaki Y, Furukawa T, Plotkin S, Koprowski H. Ultrastructural study on the sequence of human cytomegalovirus infection in human diploid cells. Arch Virol. 1973;40:311–324. doi: 10.1007/BF01242551. [DOI] [PubMed] [Google Scholar]
  • 12.Johnson DC, Schlesinger MJ. Vesicular stomatitis virus and sindbis virus glycoprotein transport to the cell surface is inhibited by ionophores. Virology. 1980;103:407–424. doi: 10.1016/0042-6822(80)90200-7. [DOI] [PubMed] [Google Scholar]
  • 13.Johnson DC, Spear PG. Monensin inhibits the processing of herpes simplex virus glycoproteins, their transport to the cell surface, and the egress of virions from infected cells. J Virol. 1982;43:1102–1112. doi: 10.1128/jvi.43.3.1102-1112.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kerr CL, Pennington TH. The effect of monensin on virion production and protein secretion in pseudorabies virus-infected cells. J Gen Virol. 1984;65:1033–1041. doi: 10.1099/0022-1317-65-6-1033. [DOI] [PubMed] [Google Scholar]
  • 15.Kääriäinen L, Hashimoto K, Saraste J, Virtanen I, Penttinen K. Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins. J Cell Biol. 1980;87:783–791. doi: 10.1083/jcb.87.3.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Lämmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T 4. Nature. 1970;227:680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  • 17.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–275. [PubMed] [Google Scholar]
  • 18.Ludwig H, Rott R. Effect of 2-deoxy-D-glucose on herpesvirus-induced inhibition of cellular DNA synthesis. J Virol. 1975;26:281–290. doi: 10.1128/jvi.16.2.217-221.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Luuokonen A, Gahmberg CG, Renkonen O. Surface labelling of Semliki forest virus glycoproteins using galactose oxidase. Virology. 1977;76:55–59. doi: 10.1016/0042-6822(77)90281-1. [DOI] [PubMed] [Google Scholar]
  • 20.Musiani M, Zerbini M. Influence of cell cycle on the efficiency of transfection with purified human cytomegalovirus DNA. Arch Virol. 1984;78:287–292. doi: 10.1007/BF01311323. [DOI] [PubMed] [Google Scholar]
  • 21.Niemann H, Boschek B, Evans E, Rosing M, Tamura T, Klenk HD. Post-translational glycosylation of corona-virus glycoprotein E 1: inhibition by monensin. EMBO J. 1982;1:1499–1504. doi: 10.1002/j.1460-2075.1982.tb01346.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Norrild B, Virtanen I, Pedersen B, Pereira L. Requirements for transport of HSV-1 glycoproteins to the cell surface membrane of human fibroblasts and vero cells. Arch Virol. 1983;77:155–166. doi: 10.1007/BF01309264. [DOI] [PubMed] [Google Scholar]
  • 23.Nowak B, Sullivan C, Sarnow P, Thomas R, Bricout F, Nicolas JC, Fleckenstein B, Levine AJ. Characterisation of monoclonal antibodies and polyclonal immune sera directed against human cytomegalovirus virion proteins. Virology. 1984;132:325–338. doi: 10.1016/0042-6822(84)90039-4. [DOI] [PubMed] [Google Scholar]
  • 24.Payne LG, Kristensson K. The effect of cytochalasin D and monensin on enveloped vaccinia virus release. Arch Virol. 1982;74:11–20. doi: 10.1007/BF01320778. [DOI] [PubMed] [Google Scholar]
  • 25.Pereira L, Hoffman M, Tatsuno M, Dondero D. Polymorphism of human cytomegalovirus glycoproteins characterized by monoclonal antibodies. Virology. 1984;139:73–86. doi: 10.1016/0042-6822(84)90331-3. [DOI] [PubMed] [Google Scholar]
  • 26.Radsak K. Effect of herpes simplex virus type 1 infection on the cellular DNA polymerase activities of mouse cell cultures. J Gen Virol. 1978;41:479–491. doi: 10.1099/0022-1317-41-3-479. [DOI] [PubMed] [Google Scholar]
  • 27.Radsak K, Furukawa T, Plotkin S. DNA synthesis in chromatin preparations from human fibroblasts infected by cytomegalovirus. Arch Virol. 1980;65:45–54. doi: 10.1007/BF01340539. [DOI] [PubMed] [Google Scholar]
  • 28.Radsak K, Weder D. Effect of 2-deoxy-D-glucose on cytomegalovirus-induced DNA synthesis in human fibroblasts. J Gen Virol. 1981;57:33–42. doi: 10.1099/0022-1317-57-1-33. [DOI] [PubMed] [Google Scholar]
  • 29.Radsak K, Mertensmeier I, Kaiser C, Wagner C. Distinction of viral and host-derived glycopolypeptides induced by “early” functions of human cytomegalovirus. Arch Virol. 1985;85:217–230. doi: 10.1007/BF01314233. [DOI] [PubMed] [Google Scholar]
  • 30.Radsak K, Wiegandt H, Unterdörfer U, Wagner C, Kaiser CJ. Sodium butyrate selectivly inhibits host cell glycoprotein synthesis in human fibroblasts infected with cytomegalovirus. Biosci Rep. 1985;5:589–599. doi: 10.1007/BF01117072. [DOI] [PubMed] [Google Scholar]
  • 31.Radsak K, Schmitz B. Unimpaired histon synthesis in human fibroblasts infected by human cytomegalovirus. Med Microbiol Immunol (Berl) 1980;168:63–72. doi: 10.1007/BF02121653. [DOI] [PubMed] [Google Scholar]
  • 32.Rasmussen L, Mullenax J, Nelson R, Merigan TC. Viral polypeptides detected by a complement-dependent neutralizing murine monoclonal antibody to human cytomegalovirus. J Virol. 1985;55:274–280. doi: 10.1128/jvi.55.2.274-280.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Saito M, Saito M, Rosenberg A. Action of monensin, a monovalent cationophore, on cultured human fibroblasts: evidence that it induces high cellular accumulation of glucosyl- and lactosylceramide (gluco- and lactocerebroside) Biochemistry. 1984;23:1043–1046. doi: 10.1021/bi00301a001. [DOI] [PubMed] [Google Scholar]
  • 34.Scholtissek C. Inhibition of multiplication of enveloped viruses by glucose derivatives. Curr Top Microbiol Immunol. 1975;70:101–119. doi: 10.1007/978-3-642-66101-3_4. [DOI] [PubMed] [Google Scholar]
  • 35.Stinski M. synthesis of proteins and glycoproteins in cells infected with human cytomegalovirus. J Virol. 1977;23:1023–1034. doi: 10.1128/jvi.23.3.751-767.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Tartakoff AM. Pertubation of vesicular traffic with the carboxylic ionophore monensin. Cell. 1983;32:1026–1028. doi: 10.1016/0092-8674(83)90286-6. [DOI] [PubMed] [Google Scholar]
  • 37.Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 1979;76:4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Van Drunen Little, Van den Hurk S, Babiuk LA. Effect of tunicamycin and monensin on biosynthesis, transport and maturation of bovine herpesvirus type 1 glycoproteins. Virology. 1985;143:104–118. doi: 10.1016/0042-6822(85)90100-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Weder D, Radsak K. Induction of a host-specific chromatin-associated glycopolypeptide by human cytomegalovirus. J Gen Virol. 1983;64:2749–2761. doi: 10.1099/0022-1317-64-12-2749. [DOI] [PubMed] [Google Scholar]
  • 40.Weiner D, Gibson W, Fields KL. Anti-complement immunofluorescence establishes nuclear localisation of human cytomegalovirus matrix protein. Virology. 1985;147:19–28. doi: 10.1016/0042-6822(85)90223-5. [DOI] [PubMed] [Google Scholar]
  • 41.Weissbach A, Hong S, Aucker J, Muller R. Characterization of herpes simplex virus induced deoxyribonucleic acid polymerase. J Biol Chem. 1973;248:6270–6277. [PubMed] [Google Scholar]
  • 42.Wenske EA, Bratton MW, Courtney RJ. Endo-β-N-acetylglucosaminidase H sensitivity of precursor to herpes simplex virus type 1 glycoproteins gB and gC. J Virol. 1982;44:241–248. doi: 10.1128/jvi.44.1.241-248.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

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