Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 58, Issue 2

Comparison of Thymidine Kinase Activities Induced in Cells Productively Infected with Herpesvirus Saimiri and Herpes Simplex Virus No Access

Abstract

SUMMARY

The replication of unselected strains of herpesvirus saimiri (HVS) was sensitive to bromodeoxyuridine and bromovinyldeoxyuridine (BVdU) but insensitive to acycloguanosine (ACG), in contrast to the growth of herpes simplex virus (HSV) which was sensitive to all three analogues. Mutants of HVS resistant to bromodeoxyuridine and BVdU could be selected by growth in the presence of these inhibitors. Productive infections of owl monkey kidney or Vero cell cultures by unselected strains of HVS resulted in increases in a thymidine kinase (TK) activity which was deficient in cells infected with bromodeoxyuridine-resistant mutants of the virus. Induction of the virus enzyme promoted a net increase in the uptake and incorporation of exogenous labelled thymidine in the face of the progressive inhibition of the overall incorporation of [S]methionine and [H]uridine into productively infected cells. The TK induced in cells infected with HVS differed from the major activity of uninfected cells and resembled that encoded by HSV in its capacity to phosphorylate iododeoxyuridine and in the sensitivity of all the thymidine phosphorylating activity to competition by BVdU. However, in contrast to the HSV TK, which phosphorylated deoxycytidine and iododeoxycytidine relatively efficiently and was sensitive to ACG, the HVS enzyme did not phosphorylate deoxycytidine or iododeoxycytidine and was insensitive to ACG. Whilst HVS, therefore, shares the characteristic of other members of the herpesvirus group of inducing a novel TK, the properties of the HVS-induced enzyme differ significantly from the enzyme of the prototype herpesvirus, HSV. The properties of the HVS TK are nonetheless sufficiently distinct from those of the uninfected cell to provide a possible basis for selective antiviral chemotherapy based on preferential phosphorylation of nucleoside analogues such as BVdU by infected cells.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): bromovinyldeoxyuridine , herpesvirus saimiri , iododeoxyuridine and thymidine kinase
© Journal of General Virology 1982
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-58-2-237
1982-02-01
2025-05-22
Loading full text...

Full text loading...

References

  1. Allaudeen H. S., Kozarich J. W., Bertino J. R., De Clercq E. 1981; On the mechanism of selective inhibition of herpesvirus replication by (E)-5-(2-bromovinyl)-2′-deoxy uridine. Proceedings of the National Academy of Sciences of the United States of America 78:2698–2802
     [Google Scholar]
  2. Allen G. P., Mcgowan J. J., Randall C. C., Mancini W., Cheng Y.-C., Gentry G. A. 1979; Purification and characterization of deoxythymidine kinase (dTK) induced in dTK 3T3 mouse cells by equine herpesvirus type 1 (EHV-1). Virology 92:367–374
     [Google Scholar]
  3. Biron K. K., Elion G. B. 1980; In vitro susceptibility of varicella-zoster virus to acyclovir. Antimicrobial Agents and Chemotherapy 18:443–447
     [Google Scholar]
  4. Boulter E. A. 1980; Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir. British Medical Journal 280:681
     [Google Scholar]
  5. Chen S. T., Estes J. E., Huang E. S., Pagano J. S. 1978; Epstein Barr virus associated thymidine kinase. Journal of Virology 26:203–208
     [Google Scholar]
  6. Coen D. M., Schaffer P. A. 1980; Two distinct loci confer resistance to acycloguanosine in herpes simplex type 1. Proceedings of the National Academy of Sciences of the United States of America 77:2265–2269
     [Google Scholar]
  7. Colby B. M., Furman P. A., Shaw J. E., Elion G. B., Pagano J. S. 1981; Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines. Journal of Virology 38:606–611
     [Google Scholar]
  8. Collins P., Bauer D. J. 1979; The activity in vitro against herpes virus of 9(2-hydroxyethoxymethylguanine (acycloguanosine), a new antiviral agent. Journal of Antimicrobial Chemotherapy 5:431–436
     [Google Scholar]
  9. Cooper G. M. 1973; Phosphorylation of 5-bromodeoxycytidine in cells infected with herpes simplex virus. Proceedings of the National Academy of Sciences of the United States of America 70:3788–3792
     [Google Scholar]
  10. Crumpacker C. S., Schnipper L. E., Zair J. A., Levin M. J. 1979; Growth inhibition by acycloguanosine of herpes virus isolated from human infections. Antimicrobial Agents and Chemotherapy 15:642–645
     [Google Scholar]
  11. Crumpacker C. S., Chartrand P., Subak-Sharpe J. H., Wilkie N. M. 1980; Resistance of herpes simplex virus to acycloguanosine – genetic and physical analysis. Virology 105:171–184
     [Google Scholar]
  12. Daniel M. D., Silva D., Jackson D., Sehgal P., Baggs R. B., Hunt R. D., Melendez L. V. 1975; Reactivation of squirrel monkey heart isolate (Herpesvirus saimiri strain) from latently infected human cell cultures and induction of malignant lymphoma in marmoset monkeys. In Comparative Leukemia Research, 1975 Bibliographa Haematologia, 1976 No. 43 pp 392–395 Edited by Clemmeson J., Yohn D. S. Basel: S. Karger;
     [Google Scholar]
  13. Darby G., Larder B. A., Bastow K. F., Field H. J. 1980; Sensitivity of viruses to phosphorylated 9-(2-hydroxyethoxymethyl) guanine revealed in TK-transformed cells. Journal of General Virology 48:451–454
     [Google Scholar]
  14. Darby G., Field H. J., Salisbury S. A. 1981; Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir resistance. Nature, London 289:81
     [Google Scholar]
  15. De Clercq E., Descamps J., DE Somes P., Barr P. J., Jones A. S., Walker R. T. 1979; (E)-5-(2-bromovinyl)-2′-deoxyuridine: a potent and selective antiherpes agent. Proceedings of the National Academy of Sciences of the United States of America 76:2947–2951
     [Google Scholar]
  16. Deinhardt F. 1973; Herpesvirus saimiri. In The Herpesviruses pp 595–625 Edited by Kaplan A. S. New York & London: Academic Press;
     [Google Scholar]
  17. Dobersen M. J., Jerkofsky M., Greer S. 1976; Enzymatic basis for the selective inhibition of varicella-zoster virus by 5-halogenated analogues of deoxycytidine. Journal of Virology 20:478–486
     [Google Scholar]
  18. Dubbs D. R., Kit S. 1964; Mutant strains of herpes simplex deficient in thymidine kinase-inducing ability. Virology 22:493–502
     [Google Scholar]
  19. Elion G. B., Furman P. A., Fyfe J. A., De Miranda P., BEauchamP L., Schaeffer H. J. 1977; Selectivity of action of an antiherpetic agent, 9(2-hydroxyethoxymethyl)guanine. Proceedings of the National Academy of Sciences of the United States of America 74:5716–5720
     [Google Scholar]
  20. Field H. J., Darby G., Wildy P. 1980; Isolation and characterization of acyclovir-resistant mutants of herpes simplex virus. Journal of General Virology 49:115–124
     [Google Scholar]
  21. Fleckenstein B. 1979; Oncogenic herpesviruses of non-human primates. Biochimica et Biophysica Acta 560:301–343
     [Google Scholar]
  22. Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. 1978; Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compounds, 9(2-hydroxyethoxymethyl)guanine. Journal of Biological Chemistry 253:8721–8727
     [Google Scholar]
  23. Hampar B., Derge J. G., Martos L. M., Walker J. L. 1972; Synthesis of Epstein-Barr virus after activation of the viral genome in a ‘virus negative’ human lymphoblastoid cell (Raji) made resistant to 5-bromodeoxyuridine. Proceedings of the National Academy of Sciences of the United States of America 69:78–82
     [Google Scholar]
  24. Honess R. W., Watson D. H. 1977a; Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. Journal of Virology 21:584–600
     [Google Scholar]
  25. Honess R. W., Watson D. H. 1977b; Unity and diversity in the herpesviruses. Journal of General Virology 37:15–37
     [Google Scholar]
  26. Honess R. W., Buchan A., Halliburton I. W., Watson D. H. 1980; Recombination and linkage between structural and regulatory genes of herpes simplex virus type 1: study of the functional organization of the genome. Journal of Virology 34:716–742
     [Google Scholar]
  27. Hunt R. D., Garcia F. G., Barahona H. H., King N. W., Fraser C. E. O., Melendez L. V. 1973; Spontaneous herpesvirus saimiri lymphoma in an owl monkey. Journal of Infectious Diseases 127:723–725
     [Google Scholar]
  28. Jamieson A. T., Subak-Sharpe J. H. 1974; Biochemical studies on the herpes simplex virus-specified deoxypyrimidine kinase activity. Journal of General Virology 24:481–492
     [Google Scholar]
  29. Jamieson A. T., Gentry G. A., Subak-Sharpe J. H. 1974; Induction of both thymidine and deoxycytidine kinase activity by herpes viruses. Journal of General Virology 24:465–480
     [Google Scholar]
  30. Leung W. C., Dubbs D. R., Trkula D., Kit S. 1975; Mitochondrial and herpesvirus specified deoxypyrimidine kinases. Journal of Virology 16:486–497
     [Google Scholar]
  31. Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951; Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193:265–275
     [Google Scholar]
  32. Mcknight S. L. 1980; The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Research 8:5949–5964
     [Google Scholar]
  33. Mcknight S. L., Gavis E. R. 1980; Expression of the herpes thymidine kinase gene in Xenopus laevis oocytes: an assay for the study of deletion mutants constructed in vitro. Nucleic Acids Research 8:5931–5948
     [Google Scholar]
  34. Minson A. C., Wildy P., Buchan A., Darby G. 1978; Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA. Cell 13:581–587
     [Google Scholar]
  35. Pereira L., Cassai E., Honess R. W., Roizman B., Terni M., Nahmias A. 1976; Variability in the structural polypeptides of herpes simplex virus 1 strains: potential application in molecular epidemiology. Infection and Immunity 13:211–220
     [Google Scholar]
  36. Schaffer P. A., Falk L. A., Deinhardt F. 1975; Attenuation of Herpesvirus saimiri for marmosets after successive passage in cell culture at 39 °C. Journal of the National Cancer Institute 55:1243–1246
     [Google Scholar]
  37. Schnipper L. E., Crumpacker C. S. 1980; Resistance of herpes simplex virus to acycloguanosine: role of virus thymidine kinase and DNA polymerase loci. Proceedings of the National Academy of Sciences of the United States of America 77:2270–2273
     [Google Scholar]
  38. Smiley J. R., Wagner M. J., Summers W. P., Summers W. C. 1980; Genetic and physical evidence for the polarity of transcription of the thymidine kinase gene of herpes simplex virus. Virology 102:83–93
     [Google Scholar]
  39. Summers W. C., Summers W. P. 1977; [125I]Deoxycytidine used in a rapid, sensitive and specific assay for herpes simplex virus type 1 thymidine kinase. Journal of Virology 24:314–318
     [Google Scholar]
  40. Wigler M., Silverstein S., Lee L. S., Pellicer A., Cheng Y. C., Axel T. 1977; Transfer of purified herpes virus thymidine kinase to cultured mouse cells. Cell 11:223–232
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-58-2-237
Loading
Comparison of Thymidine Kinase Activities Induced in Cells Productively Infected with Herpesvirus Saimiri and Herpes Simplex Virus
J. Gen. Virol. 58, 237 (1982); https://doi.org/10.1099/0022-1317-58-2-237
/content/journal/jgv/10.1099/0022-1317-58-2-237
/content/journal/jgv/10.1099/0022-1317-58-2-237
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error