1887

Abstract

Summary

5-Azacytidine (5-AZC) reduces cytosine methylation in DNA and has been reported to activate quiescent virus genes. Treatment of explant cultures of latently herpes simplex virus type 2 (HSV-2)-infected guinea-pig dorsal root ganglia and spinal cords with 5-AZC significantly enhanced the rate of HSV recovery. Both the number of isolates from ganglia ( < 0.001) and the rate of recovery ( < 0.001) were significantly increased with the addition of 50 µ-5-AZC to explant cultures. Increased virus recovery appeared to be due to the induction of reactivation of latent virus, rather than an increase in replication, since 5-AZC inhibited HSV replication. These data support a role for methylation in HSV latency and reactivation.

Keyword(s): 5-azacytidine , HSV-2 , latency and methylation
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-69-5-1079
1988-05-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/69/5/JV0690051079.html?itemId=/content/journal/jgv/10.1099/0022-1317-69-5-1079&mimeType=html&fmt=ahah

References

  1. BEN-SASSON S. A., KLEIN G. 1981; Activation of the Epstein-Barr virus genome by 5-azacytidine in latently infected human lymphoid lines. International Journal of Cancer 28:131–135
    [Google Scholar]
  2. BERNSTEIN D. I., KAPPES J. C. Enhanced in vitro reactivation of latent herpes simplex virus from neural and peripheral tissue with hexamethylenebisacetamide. Archives of Virology in press
    [Google Scholar]
  3. BERNSTEIN D. I., STANBERRY L. R. 1986; Zosteriform spread of herpes simplex virus type 2 genital infection in the guinea-pig. Journal of General Virology 67:1851–1857
    [Google Scholar]
  4. BRESLOW N. 1970; A generalized Kruskal-Wallis test for comparing K samples subject to unequal patterns of analysis. Biometrika 57:579–594
    [Google Scholar]
  5. CHRISTY B., SCANGOS G. 1982; Expression of transferred thymidine kinase genes is controlled by methylation. Proceedings of the National Academy of Sciences, U.S.A 79:6299–6303
    [Google Scholar]
  6. CLOUGH D. W., KUNKEL L. M., DAVIDSON R. L. 1982; 5-Azacytidine-induced reactivation of a herpes simplex thymidine kinase gene. Science 216:70–73
    [Google Scholar]
  7. COMPERE S. J., PALMITER R. D. 1981; DNA methylation controls the inducibility of the mouse metallothionein-I gene in lymphoid cells. Cell 25:233–240
    [Google Scholar]
  8. DESROSIERS R. C, MULDER C., FLECKENSTEIN B. 1979; Methylation of herpesvirus saimiri DNA in lymphoid tumor cell lines. Proceedings of the National Academy of Sciences, U.S.A 76:3839–3843
    [Google Scholar]
  9. DRESSLER G. R., ROCK D. L., FRASER N. W. 1987; Latent herpes simplex virus type 1 DNA is not extensively methylated in vivo. Journal of General Virology 68:1761–1765
    [Google Scholar]
  10. HARBOUR D. A., HILL T. J., BLYTH W. A. 1983; Recurrent herpes simplex in the mouse: inflammation in the skin and activation of virus in the ganglia following peripheral stimulation. Journal of General Virology 64:1491–1498
    [Google Scholar]
  11. HILL T. J. 1984 Herpes simplex virus latency. The Herpesviruses 3175–240 Edited by Roizman B. New York & London: Plenum Press;
    [Google Scholar]
  12. HSIAO W. L. W., GATTONL-CELLI S., KIRSCHMEIER P., WEINSTEIN I. B. 1984; Effects of 5-azacytidine on methylation and expression of specific DNA sequences in C3H 10T 1/2 cells. Molecular Cell Biology 4:634–641
    [Google Scholar]
  13. HSIAO W. L. W., GATTONL-CELLI S., WEINSTEIN I. B. 1986; Effects of 5-azacytidine on expression of endogenous retrovirus related sequences in C3H and 10T 1/2 cells. Journal of Virology 57:1119–1126
    [Google Scholar]
  14. HSIUNG G. D., TENSER R. B., FONG C. K. Y. 1976; Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: growth characteristics and antigenic relationship. Infection and Immunity 13:926–933
    [Google Scholar]
  15. JAENISCH R., SCHNIEKE A., HARBERS K. 1985; Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues. Proceedings of the National Academy of Sciences, U.S.A 82:1451–1455
    [Google Scholar]
  16. JONES P. A. 1985; Altering gene expression with 5-azacytidine. Cell 40:485–486
    [Google Scholar]
  17. JONES P. A., TAYLOR S. M. 1980; Cellular differentiation, cytidine analogs and DNA methylation. Cell 20:85–93
    [Google Scholar]
  18. KORBA B. E., WILSON V. L., YOAKUM G. H. 1985; Induction of hepatitis B virus core gene in human cells by cytosine demethylation in the promoter. Science 228:1103–1106
    [Google Scholar]
  19. LASNERET J., CANIVET M., HOJMAN-MONTES DE OCA F., TOBALY J., EMANOIL-RAVICOVITCH R., PERIES J. 1983; Activation of intracisternal A particles by 5-azacytidine in mouse KI-BALB cell line. Virology 128:485–489
    [Google Scholar]
  20. LEY T. J., DESIMONE J., NOGUCHI C. T., TURNER P. H., SCHECHTER A. N., HELLER P., NIENHUIS A. W. 1983; 5- Azacytidine increases gamma-globulin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia. Blood 62:370–380
    [Google Scholar]
  21. MOMPARLER R. L., BOUCHARD J., ONETTO M., RIVARD G. E. 1984; 5-Aza-2′-deoxycytidine therapy in patients with acute leukemia inhibits DNA methylation. Leukemia Research 8:181–185
    [Google Scholar]
  22. NAVEH-MANY T., CEDAR H. 1981; Active gene sequences are undermethylated. Proceedings of the National Academy of Sciences, U.S.A 78:4246–4250
    [Google Scholar]
  23. POLLACK Y., STEIN R., RAZIN A., CEDAR H. 1980; Methylation of foreign DNA sequences in eukaryotic cells. Proceedings of the National Academy of Sciences, U.S.A 77:6463–6467
    [Google Scholar]
  24. PRICE R. W., SCHMITZ J. 1978; Reactivation of latent herpes simplex virus infection of the autonomic nervous system by postganglionic neurectomy. Infection and Immunity 19:523–529
    [Google Scholar]
  25. REICHMAN M., PENMAN S. 1973; The mechanism of inhibition of protein synthesis by 5-azacytidine in HeLa cells. Biochimica et biophysica acta 324:282–289
    [Google Scholar]
  26. SANES J. R., OKUN L. M. 1972; Induction of DNA synthesis in cultured neurons by ultraviolet light or methylmethane sulfonate. Journal of Cell Biology 53:587–590
    [Google Scholar]
  27. STANBERRY L. R., BERNSTEIN D. I., KIT S., MYERS M. 1986; Genital reinfection after recovery from initial genital infection with herpes simplex virus type 2 in guinea pigs. Journal of Infectious Diseases 153:1055–1061
    [Google Scholar]
  28. SUTTER D., DOERFLER W. 1980; Methylation of integrated adenoviral type 12 DNA sequences in transformed cells is inversely correlated with viral gene expression. Proceedings of the National Academy of Sciences, U.S.A 77:253–256
    [Google Scholar]
  29. TAYLOR S. M., JONES P. A. 1982; Mechanism of action of eukaryotic DNA methyltransferase. Use of 5-azacytosine-containing DNA. Journal of Molecular Biology 162:679–692
    [Google Scholar]
  30. VAN GROENINGEN C. J., LEYVA A., O’BRIEN A. M. P., GALL H. E., PINEDO H. M. 1986; Phase I and pharmacokinetic study of 5-aza-2′-deoxycytidine (NSC 127716) in cancer patients. Cancer Research 46:4831–4836
    [Google Scholar]
  31. WHITBY A. J., BLYTH W. A., HILL T. J. 1988; The effect of DNA hypomethylating agents on the reactivation of herpes simplex virus from latently infected mouse ganglia in vitro. Archives of Virology in press
    [Google Scholar]
  32. YOUSSOUFIAN H., HAMMER S. M., HIRSCH M. S., MULDER C. 1982; Methylation of the viral genome in an in vitro model of herpes simplex virus latency. Proceedings of the National Academy of Sciences, U.S.A 79:2207–2210
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-69-5-1079
Loading
/content/journal/jgv/10.1099/0022-1317-69-5-1079
Loading

Data & Media loading...

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