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. 1990 Jan;64(1):9–15. doi: 10.1128/jvi.64.1.9-15.1990

Human cytomegalovirus induces expression of cellular topoisomerase II.

J D Benson 1, E S Huang 1
PMCID: PMC249031  PMID: 2152837

Abstract

Previous work from our laboratory has suggested that topoisomerase II is required for replication of human cytomegalovirus (HCMV). In assays of confluent human embryonic lung cells infected with HCMV, topoisomerase II inhibitors exhibited an irreversible inhibition of viral DNA replication. However, Northern (RNA blot) and Western (immunoblot) analyses of confluent uninfected human embryonic lung cells detected very low levels of cellular topoisomerase II RNA and protein. Quantitation of human topoisomerase II RNA and protein levels at various times after HCMV infection revealed that HCMV induces increased intracellular levels of both topoisomerase II RNA and protein. Such accumulation began at early times of infection, continued through late in infection, and was not reduced by inhibition of viral DNA synthesis. This is the first report of such induction by a viral infection. Topoisomerase II was also detected in isolated HCMV virions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman P., Glover C. V., Osheroff N. Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro. Proc Natl Acad Sci U S A. 1985 May;82(10):3164–3168. doi: 10.1073/pnas.82.10.3164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benson J. D., Huang E. S. Two specific topoisomerase II inhibitors prevent replication of human cytomegalovirus DNA: an implied role in replication of the viral genome. J Virol. 1988 Dec;62(12):4797–4800. doi: 10.1128/jvi.62.12.4797-4800.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bodley A. L., Wu H. Y., Liu L. F. Regulation of DNA topoisomerases during cellular differentiation. NCI Monogr. 1987;(4):31–35. [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Colberg-Poley A. M., Santomenna L. D. Selective induction of chromosomal gene expression by human cytomegalovirus. Virology. 1988 Sep;166(1):217–228. doi: 10.1016/0042-6822(88)90163-8. [DOI] [PubMed] [Google Scholar]
  6. Davis M. G., Kenney S. C., Kamine J., Pagano J. S., Huang E. S. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8642–8646. doi: 10.1073/pnas.84.23.8642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deaven L. L., Oka M. S., Tobey R. A. Cell-cycle-specific chromosome damage following treatment of cultured Chinese hamster cells with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl. J Natl Cancer Inst. 1978 May;60(5):1155–1161. [PubMed] [Google Scholar]
  8. Deffie A. M., Batra J. K., Goldenberg G. J. Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines. Cancer Res. 1989 Jan 1;49(1):58–62. [PubMed] [Google Scholar]
  9. DiNardo S., Voelkel K., Sternglanz R. DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci U S A. 1984 May;81(9):2616–2620. doi: 10.1073/pnas.81.9.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duguet M., Lavenot C., Harper F., Mirambeau G., De Recondo A. M. DNA topoisomerases from rat liver: physiological variations. Nucleic Acids Res. 1983 Feb 25;11(4):1059–1075. doi: 10.1093/nar/11.4.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edenberg H. J. Novobiocin inhibition of simian virus 40 DNA replication. Nature. 1980 Jul 31;286(5772):529–531. doi: 10.1038/286529a0. [DOI] [PubMed] [Google Scholar]
  12. Estes J. E., Huang E. S. Stimulation of cellular thymidine kinases by human cytomegalovirus. J Virol. 1977 Oct;24(1):13–21. doi: 10.1128/jvi.24.1.13-21.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Geballe A. P., Leach F. S., Mocarski E. S. Regulation of cytomegalovirus late gene expression: gamma genes are controlled by posttranscriptional events. J Virol. 1986 Mar;57(3):864–874. doi: 10.1128/jvi.57.3.864-874.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Geballe A. P., Spaete R. R., Mocarski E. S. A cis-acting element within the 5' leader of a cytomegalovirus beta transcript determines kinetic class. Cell. 1986 Sep 12;46(6):865–872. doi: 10.1016/0092-8674(86)90068-1. [DOI] [PubMed] [Google Scholar]
  15. Goins W. F., Stinski M. F. Expression of a human cytomegalovirus late gene is posttranscriptionally regulated by a 3'-end-processing event occurring exclusively late after infection. Mol Cell Biol. 1986 Dec;6(12):4202–4213. doi: 10.1128/mcb.6.12.4202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gönczöl E., Plotkin S. A. Cells infected with human cytomegalovirus release a factor(s) that stimulates cell DNA synthesis. J Gen Virol. 1984 Oct;65(Pt 10):1833–1837. doi: 10.1099/0022-1317-65-10-1833. [DOI] [PubMed] [Google Scholar]
  18. Heck M. M., Earnshaw W. C. Topoisomerase II: A specific marker for cell proliferation. J Cell Biol. 1986 Dec;103(6 Pt 2):2569–2581. doi: 10.1083/jcb.103.6.2569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Heck M. M., Hittelman W. N., Earnshaw W. C. Differential expression of DNA topoisomerases I and II during the eukaryotic cell cycle. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1086–1090. doi: 10.1073/pnas.85.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hirai K., Watanabe Y. Induction of alpha type DNA polymerases in human cytomegalovirus-infected WI-38 cells. Biochim Biophys Acta. 1976 Oct 18;447(3):328–339. doi: 10.1016/0005-2787(76)90056-3. [DOI] [PubMed] [Google Scholar]
  21. Holm C., Goto T., Wang J. C., Botstein D. DNA topoisomerase II is required at the time of mitosis in yeast. Cell. 1985 Jun;41(2):553–563. doi: 10.1016/s0092-8674(85)80028-3. [DOI] [PubMed] [Google Scholar]
  22. Holm C., Stearns T., Botstein D. DNA topoisomerase II must act at mitosis to prevent nondisjunction and chromosome breakage. Mol Cell Biol. 1989 Jan;9(1):159–168. doi: 10.1128/mcb.9.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hsiang Y. H., Wu H. Y., Liu L. F. Proliferation-dependent regulation of DNA topoisomerase II in cultured human cells. Cancer Res. 1988 Jun 1;48(11):3230–3235. [PubMed] [Google Scholar]
  24. Hsieh T. Purification and properties of type II DNA topoisomerase from embryos of Drosophila melanogaster. Methods Enzymol. 1983;100:161–170. doi: 10.1016/0076-6879(83)00052-x. [DOI] [PubMed] [Google Scholar]
  25. Jeor S. C., Albrecht T. B., Funk F. D., Rapp F. Stimulation of cellular DNA synthesis by human cytomegalovirus. J Virol. 1974 Feb;13(2):353–362. doi: 10.1128/jvi.13.2.353-362.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liu L. F. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 1989;58:351–375. doi: 10.1146/annurev.bi.58.070189.002031. [DOI] [PubMed] [Google Scholar]
  27. Mar E. C., Cheng Y. C., Huang E. S. Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on human cytomegalovirus replication in vitro. Antimicrob Agents Chemother. 1983 Oct;24(4):518–521. doi: 10.1128/aac.24.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miskimins R., Miskimins W. K., Bernstein H., Shimizu N. Epidermal growth factor-induced topoisomerase(s). Intracellular translocation and relation to DNA synthesis. Exp Cell Res. 1983 Jun;146(1):53–62. doi: 10.1016/0014-4827(83)90323-3. [DOI] [PubMed] [Google Scholar]
  29. Nelson W. G., Cho K. R., Hsiang Y. H., Liu L. F., Coffey D. S. Growth-related elevations of DNA topoisomerase II levels found in Dunning R3327 rat prostatic adenocarcinomas. Cancer Res. 1987 Jun 15;47(12):3246–3250. [PubMed] [Google Scholar]
  30. Nelson W. G., Liu L. F., Coffey D. S. Newly replicated DNA is associated with DNA topoisomerase II in cultured rat prostatic adenocarcinoma cells. Nature. 1986 Jul 10;322(6075):187–189. doi: 10.1038/322187a0. [DOI] [PubMed] [Google Scholar]
  31. Pizzorno M. C., O'Hare P., Sha L., LaFemina R. L., Hayward G. S. trans-activation and autoregulation of gene expression by the immediate-early region 2 gene products of human cytomegalovirus. J Virol. 1988 Apr;62(4):1167–1179. doi: 10.1128/jvi.62.4.1167-1179.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Richter A., Strausfeld U., Knippers R. Effects of VM26 (teniposide), a specific inhibitor of type II DNA topoisomerase, on SV40 DNA replication in vivo. Nucleic Acids Res. 1987 Apr 24;15(8):3455–3468. doi: 10.1093/nar/15.8.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sahyoun N., Wolf M., Besterman J., Hsieh T., Sander M., LeVine H., 3rd, Chang K. J., Cuatrecasas P. Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1603–1607. doi: 10.1073/pnas.83.6.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schickedanz J., Philipson L., Ansorge W., Pepperkok R., Klein R., Koszinowski U. H. The 89,000-Mr murine cytomegalovirus immediate-early protein stimulates c-fos expression and cellular DNA synthesis. J Virol. 1988 Sep;62(9):3341–3347. doi: 10.1128/jvi.62.9.3341-3347.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Snapka R. M., Powelson M. A., Strayer J. M. Swiveling and decatenation of replicating simian virus 40 genomes in vivo. Mol Cell Biol. 1988 Feb;8(2):515–521. doi: 10.1128/mcb.8.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Snapka R. M. Topoisomerase inhibitors can selectively interfere with different stages of simian virus 40 DNA replication. Mol Cell Biol. 1986 Dec;6(12):4221–4227. doi: 10.1128/mcb.6.12.4221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Spivack J. G., O'Boyle D. R., 2nd, Fraser N. W. Novobiocin and coumermycin A1 inhibit viral replication and the reactivation of herpes simplex virus type 1 from the trigeminal ganglia of latently infected mice. J Virol. 1987 Oct;61(10):3288–3291. doi: 10.1128/jvi.61.10.3288-3291.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tanaka S., Ihara S., Watanabe Y. Human cytomegalovirus induces DNA-dependent RNA polymerases in human diploid cells. Virology. 1978 Aug;89(1):179–185. doi: 10.1016/0042-6822(78)90050-8. [DOI] [PubMed] [Google Scholar]
  39. Taudou G., Mirambeau G., Lavenot C., der Garabedian A., Vermeersch J., Duguet M. DNA topoisomerase activities in concanavalin A-stimulated lymphocytes. FEBS Lett. 1984 Oct 29;176(2):431–435. doi: 10.1016/0014-5793(84)81212-0. [DOI] [PubMed] [Google Scholar]
  40. Tewey K. M., Chen G. L., Nelson E. M., Liu L. F. Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Jul 25;259(14):9182–9187. [PubMed] [Google Scholar]
  41. Tobey R. A., Deaven L. L., Oka M. S. Kinetic response of cultured Chinese hamster cells to treatment with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl. J Natl Cancer Inst. 1978 May;60(5):1147–1153. doi: 10.1093/jnci/60.5.1147. [DOI] [PubMed] [Google Scholar]
  42. Uemura T., Yanagida M. Isolation of type I and II DNA topoisomerase mutants from fission yeast: single and double mutants show different phenotypes in cell growth and chromatin organization. EMBO J. 1984 Aug;3(8):1737–1744. doi: 10.1002/j.1460-2075.1984.tb02040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  44. West C., Stratford I. J., Barrass N., Smith E. A comparison of adriamycin and mAMSA in vitro: cell lethality and SCE studies. Br J Cancer. 1981 Dec;44(6):798–809. doi: 10.1038/bjc.1981.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yang L., Wold M. S., Li J. J., Kelly T. J., Liu L. F. Roles of DNA topoisomerases in simian virus 40 DNA replication in vitro. Proc Natl Acad Sci U S A. 1987 Feb;84(4):950–954. doi: 10.1073/pnas.84.4.950. [DOI] [PMC free article] [PubMed] [Google Scholar]

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