1887

Abstract

Inhibitors of myristoylation and analogues of myristic acid inhibit the replication of some retroviruses including human immunodeficiency virus, but no studies with other virus families have been reported. We have shown that replication of varicella-zoster virus (VZV) in tissue is inhibited by -2-hydroxymyristic acid at concentrations similar to those required for inhibition with acyclovir. Protein synthesis is not inhibited, but protein myristoylation is non-specifically reduced. Despite this lack of specificity, -2-hydroxymyristic acid inhibits VZV replication without apparent cytotoxicity. This is in agreement with our earlier suggestion that non-specific inhibitors of myristoylation could have antiviral effects without toxicity to cells due to the stability of cellular myristoylproteins. This supports suggestions that myristoylation inhibitors have potential as antiviral drugs against the many viruses that produce myristoylproteins.

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1993-06-01
2023-01-29
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References

  1. Bonner W. M., Laskey R. A. 1974; A film detection method for tritium labelled proteins and nucleic acids in polyacrylamide gels. European Journal of Biochemistry 46:83–88
    [Google Scholar]
  2. Boyd M. R., Bacon T. H., Sutton D., Cole M. 1987; Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxy-methylbut-l-yl)guanine (BRL 39123) in cell culture. Antimicrobial Agents and Chemotherapy 31:1238–1242
    [Google Scholar]
  3. Bryant M., Ratner L. 1990; Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proceedings of the National Academy of Sciences, U.S.A. 87:523–527
    [Google Scholar]
  4. Bryant M. L., Heuckeroth R. O., Kimata J. T., Ratner L., Gordon J. I. 1989; Replication of human immunodeficiency virus 1 and Moloney murine leukemia virus is inhibited by different heteroatom-containing analogs of myristic acid. Proceedings of the National Academy of Sciences, U.S.A. 86:8655–8699
    [Google Scholar]
  5. Bryant M. L., Ratner L., Duronio R. J., Kishore N. S., Devadas B., Adams S. P., Gordon J. I. 1991; Incorporation of 12-methoxydodecanoate into the human immunodeficiency virus 1 gag polyprotein precursor inhibits its proteolytic processing and virus production in a chronically infected cell line. Proceedings of the National Academy of Sciences, U.S.A. 88:2055–2059
    [Google Scholar]
  6. Devadas B., Lu T., Katoh A., Kishore N. S., Wade A. C., Mehta P. P., Rudnick D. A., Bryant M. L., Adams S. P., Li Q., Gokel G. W., Gordon J. I. 1992; Substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein V-myristoyltransferase. Journal of Biological Chemistry 267:7224–7239
    [Google Scholar]
  7. Grose C., Brunell P. A. 1978; Varicella-zoster virus: isolation and propagation in human melanoma cells at 36 °C and 32 °C. Infection and Immunity 19:199–203
    [Google Scholar]
  8. Harper D. R., Gilbert R. L. 1992; Viral lipoproteins. Reviews in Medical Virology 2:107–115
    [Google Scholar]
  9. Harper D. R., Kangro H. O. 1990; Lipoproteins of varicella-zoster virus. Journal of General Virology 71:459–463
    [Google Scholar]
  10. Harper D. R., Kangro H. O., Heath R. B. 1990; Serological responses in varicella and zoster assayed by immunoblotting. Journal of Medical Virology 30:61–67
    [Google Scholar]
  11. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227:680–685
    [Google Scholar]
  12. McIlhinney R. A. J. 1990; The fats of life: the importance and function of protein acylation. Trends in Biochemical Sciences 15:387–391
    [Google Scholar]
  13. Marc D., Drugeon G., Haenni A. L., Girard M., Van Der Werf S. 1989; Role of myristoylation of poliovirus capsid protein VP4 as determined by site-directed mutagenesis of its N-terminal sequence. EMBO Journal 8:2661–2668
    [Google Scholar]
  14. Matthews J. A., Batki A., Hynds C., Kricka L. J. 1985; Enhanced chemiluminescent method for the detection of DNA dot-hybridization assays. Analytical Biochemistry 151:205–209
    [Google Scholar]
  15. Paige L. A., Zheng G. Q., DeFrees S. A., Cassady J. M., Geahlen R. L. 1990; Metabolic activation of 2-substituted derivatives of myristic acid to form potent inhibitors of myristoyl CoA: protein IV-myristoyl transferase. Biochemistry 29:10566–10573
    [Google Scholar]
  16. Saermark T., Kleinschmitt A., Wulff A. M., Andreassen H., Magee A., Erfle V. 1991; Characterization of TV-myristoyl transferase inhibitors and their effect on HIV release. AIDS 5:951–958
    [Google Scholar]
  17. Schmidt M. F. G. 1989; Fatty acylation of proteins. Biochimica et biophysica acta 988:411–126
    [Google Scholar]
  18. Streuli C. H., Griffin B. E. 1987; Myristic acid is coupled to a structural protein of polyoma virus and SV40. Nature, London 326:619–622
    [Google Scholar]
  19. Tashiro A., Shoji S., Kubota Y. 1990; Antimyristoylation of the gag proteins in the human immunodeficiency virus-infected cells with A-myristoyl glycinal diethylacetal resulted in inhibition of virus production. Biochemical and Biophysical Research Communications 165:1145–1154
    [Google Scholar]
  20. Towler D. A., Gordon J. L., Adams S. P., Glaser L. 1988; The biology and biochemistry of eukaryotic protein acylation. Annual Review of Biochemistry 57:69–99
    [Google Scholar]
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