1887

Abstract

SUMMARY

Four nucleoside analogues, 1-(2′-deoxy-2′-fluoro-β--arabinofuranosyl)-5-methyluracil(FMAU), -5-iodouracil (FIAU), -5-methylcytosine (FMAC) and -5-iodocytosine (FIAC), were studied for their effect on human cytomegalovirus (HCMV) replication . FMAU, FIAU, FMAC and FIAC showed antiviral activities for four strains of HCMV (Major, Clegg, D and Towne) in a plaque reduction asssay, with a dose required for 50% inhibition (ED) in the range of 0.1 to 0.65 µ. At a concentration of 1 µ-FMAU or -FIAC, the synthesis of five virus-specific late polypeptides of molecular weights 150000, 120000, 67000, 54000 and 27000 was entirely blocked. Quantification of Towne viral DNA synthesis, using complementary RNA-DNA hybridization with a Towne-specific cRNA probe, demonstrated a complete inhibition of HCMV DNA replication at 1 µ of FMAU or FIAC. After the removal of the inhibitors, however, viral DNA synthesis resumed, and infectious virus reappeared, indicating that the inhibition of HCMV replication by these nucleoside analogues was of a virostatic reversible type.

Keyword(s): CMV , inhibition and nucleoside analogues
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-65-1-47
1984-01-01
2021-10-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/65/1/JV0650010047.html?itemId=/content/journal/jgv/10.1099/0022-1317-65-1-47&mimeType=html&fmt=ahah

References

  1. Camiener G. W. 1968; Studies of the enzymatic deamination of aracytidine. V. Inhibition in vitro and in vivo by tetrahydrouridine and other reduced pyrimidine nucleosides. Biochemical Pharmacology 17:1981–1991
    [Google Scholar]
  2. Cheng Y. C., Dutschman G., Fox J. J., Watanabe K. A., Machida H. 1981; Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinase. Antimicrobial Agents and Chemotherapy 20:420–423
    [Google Scholar]
  3. Chou T. C., Lopez C., Colacino J. M., Philips F. S. 1980; Metabolism and effects of 2′-fluoro-5-iodo-l-β-d-arabinofuranosylcytosine (FIAC) in human leukemic and virus-infected Vero cells. Proceedings of the American Association for Cancer Research 21:269
    [Google Scholar]
  4. Cohen R. M., Wolfenden R. 1971; Cytidine deaminase from Escherichia coli. Purification, properties, and inhibition by the potential transition state analog 3, 4, 5, 6-tetrahydrouridine. Journal of Biological Chemistry 246:7561–7565
    [Google Scholar]
  5. Crumpacker C. S., Schnipper L. E., Zaia J. A., Levin M. J. 1979; Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Antimicrobial Agents and Chemotherapy 15:642–645
    [Google Scholar]
  6. Elion G. B., Furman P. A., Fyfe J. A., Demiranda 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, U. S. A 74:5716–5720
    [Google Scholar]
  7. Estes J., Huang E. S. 1977; Stimulation of cellular thymidine kinase by human cytomegalovirus. Journal of Virology 24:13–21
    [Google Scholar]
  8. Fox J. J., Lopez C., Watanabe K. A. 1981; 2′-Fluoro-arabinosyl pyrimidine nucleosides: chemistry, antiviral, and potential anticancer activities. In Medicinal Chemistry Advances pp 27–40 Edited by De Las Heras F. G., Vega S. Oxford & New York: Pergamon Press;
    [Google Scholar]
  9. Gillespie D., Spiegelman S. 1965; A quantitative assay for DNA-RNA hybrids with DNA immobilized on a membrane. Journal of Molecular Biology 12:829–842
    [Google Scholar]
  10. Hanze A. R. 1967; Nucleic acids. IV. The catalytic reduction of pyrimidine nucleosides (human liver deaminase inhibition). Journal of the American Chemical Society 89:6720–6725
    [Google Scholar]
  11. Huang E. S. 1975; Human cytomegalovirus. IV. Specific inhibition of virus-induced DNA polymerase activity and viral DNA replication by phosphonoacetic acid. Journal of Virology 16:1560–1565
    [Google Scholar]
  12. Huang E. S., Chen S. T., Pagano J. S. 1973; Human cytomegalovirus. I. Purification and characterization of viral DNA. Journal of Virology 12:1473–1481
    [Google Scholar]
  13. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227:680–685
    [Google Scholar]
  14. Lopez C., Livelli T., Watanabe K., Reichman U., Fox I. J. 1979; ′-Fluoro-5-iodo-aracytosine: a potent antiherpesvirus nucleoside with minimum toxicity to normal cells. Proceedings of the American Association for Cancer Research 20:183
    [Google Scholar]
  15. Lopez C. K., Watanabe K. A., Fox J. J. 1980; 2′-Fluoro-5-iodo-aracytosine, a potent and selective antiherpesvirus agent. Antimicrobial Agents and Chemotherapy 17:803–806
    [Google Scholar]
  16. Mar E. C., Patel P. C., Huang E. S. 1981; Human cytomegalovirus-associated DNA polymerase and protein kinase activities. Journal of General Virology 57:149–156
    [Google Scholar]
  17. Mar E. C., Patel P. C., Huang E. S. 1982; Effect of 9-(2-hydroxyethoxymethyl)guanine on viral-specific polypeptide synthesis in human cytomegalovirus-infected cells. American Journal of Medicine 73:82–85
    [Google Scholar]
  18. Neil G., Moxley T., Manak R. 1970; Enhancement by tetrahydrouridine of I-/J-D-arabinofuranosylcytosine (cytarabine) oral activity in L1210 leukemic mice. Cancer Research 30:2166–2172
    [Google Scholar]
  19. Philips F. S., Vidal P., Grant A. J., Reichman U., Watanabe K. A., Fox I. J., Chou T. C. 1980; Distribution and metabolic fate of a new antiviral nucleoside: 2′-fiuoro-5-iodo-1-β-arabino-furanosylcytosine (FIAC). Proceedings of the American Association for Cancer Research 21:269
    [Google Scholar]
  20. Watanabe K. A., Reichman U., Hioroto K., Lopez C., Fox J. 1979; Nucleosides. 110. Synthesis and antiherpes virus activity of some 5-fluoro-2′-deoxyarabinofuranosylpyrimidine nucleosides. Journal of Medicinal Chemistry 22:21–24
    [Google Scholar]
  21. Zavada V., Erban V., Rezacova D., Vonka V. 1976; Thymidine kinase in cytomegalovirus infected cells. Archives of Virology 52:333–339
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-65-1-47
Loading
/content/journal/jgv/10.1099/0022-1317-65-1-47
Loading

Data & Media loading...

Most cited this month 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