1887

Abstract

SUMMARY

Complementation between phosphonoacetic acid (PAA)-resistant ( ) and -sensitive ( ) variants of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was studied to provide information on the function of the virus-coded DNA polymerase. Complementation within and between serotypes was demonstrated, with the growth of the partner in mixed infections becoming relatively more resistant and the partner relatively more sensitive to PAA than in the corresponding single infections. However, the relative contribution of the partner to the mixed infection had a disproportionately large effect on the resultant sensitivity of the mixed infection which was incompatible with non-interactive (e.g. monomeric) polymerase molecules as determinants of PAA sensitivity and resistance. Although a number of solutions gave equally good fits to the available data, the simplest was obtained by assuming that the functional DNA polymerase was a trimer and that only the ( ) homotrimer was active in the presence of the drug. In addition, yields from mixed infections in the presence of PAA were enriched for the resistant partner relative to yields in the absence of the drug. These latter results suggested that the intracellular distribution of resistant DNA polymerase oligomers was non-random with respect to resistant and sensitive template genomes and that these resistant polymerase molecules were more likely to encounter and replicate resistant than sensitive genomes. Such an explanation seems to require vectorial nuclear-cytoplasm-nucleus translocation and restricted diffusion of transcript and gene products determining resistance.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-57-2-297
1981-12-01
2022-08-10
Loading full text...

Full text loading...

/deliver/fulltext/jgv/57/2/JV0570020297.html?itemId=/content/journal/jgv/10.1099/0022-1317-57-2-297&mimeType=html&fmt=ahah

References

  1. Chartrand P., Stow N. D., Timbury M. C., Wilkie N. M. 1979; Physical mapping of paar mutations of herpes simplex virus type 1 and type 2 by intertypic marker rescue. Journal of Virology 31:265–276
    [Google Scholar]
  2. Chartrand P., Crumpacker C. S., Schaffer P. A., Wilkie N. M. 1980; Physical and genetic analysis of the herpes simplex virus DNA polymerase locus. Virology 103:311–326
    [Google Scholar]
  3. 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]
  4. Dubbs D. R., Kit S. 1964; Mutant strains of herpes simplex virus deficient in thymidine kinase inducing activity. Virology 22:493–502
    [Google Scholar]
  5. Erikkson B., Larsson A., Helostrand E., Johansson N.-G., Ӧberg B. 1980; Pyrophosphate analogues as inhibitors of herpes simplex virus type 1 DNA polymerase. Biochimica et Biophysica Acta 607:53–64
    [Google Scholar]
  6. Herrin T. R., Fairgrieve J. S., Bower R. R., Shipkowitz N. L., Mao J. C-H. 1977; Synthesis and antiherpes activity of analogues of phosphonoacetic acid. Journal of Medicinal Chemistry 20:660–663
    [Google Scholar]
  7. Honess R. W., Watson D. H. 1977; Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. Journal of Virology 21:584–600
    [Google Scholar]
  8. 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]
  9. Knopf K.-W. 1979; Properties of herpes simplex virus DNA polymerase and characterization of its associated exonuclease activity. European Journal of Biochemistry 98:231–244
    [Google Scholar]
  10. Leinbach S., Reno J. M., Lee L. F., Isbell A. F., Boezi J. A. 1976; Mechanism of phosphonoacetic acid inhibition of herpes virus induced DNA polymerase. Biochemistry 15:426–430
    [Google Scholar]
  11. Ostrander M., Cheng Y.-C. 1980; Properties of herpes simplex virus type 1 and type 2 DNA polymerase. Biochimica et Biophysica Acta 609:232–245
    [Google Scholar]
  12. Overby L. R., Robishaw E. E., Scheicher J. B., Reuter A., Shipkowitz N. L., Mao J. C-H. 1974; Inhibition of herpes simplex virus replication by phosphonoacetic acid. Antimicrobial Agents and Chemotherapy 6:360–365
    [Google Scholar]
  13. Powell K. L., Purifoy D. J. M. 1977; Nonstructural proteins of herpes simplex virus. I. Purification of the induced DNA polymerase. Journal of Virology 24:618–626
    [Google Scholar]
  14. Purifoy D. J. M., Powell K. L. 1977; Herpes simplex virus DNA polymerase as the site of phosphonoacetate sensitivity: temperature-sensitive mutants. Journal of Virology 24:470–477
    [Google Scholar]
  15. Purifoy D. J. M., Powell K. L. 1981; Temperature-sensitive mutants in two distinct complementation groups of herpes simplex virus type 1 specify thermolabile DNA polymerase. Journal of General Virology 54:219–222
    [Google Scholar]
  16. Reno J. M., Lee L. P., Boezi J. A. 1978; Inhibition of herpesvirus regulation and herpesvirus-induced deoxyribonucleic acid polymerase by phosphonoformate. Antimicrobial Agents and Chemotherapy 13:188–192
    [Google Scholar]
  17. Russell W. C. 1962; A sensitive and precise plaque assay for herpes virus. Nature, London 195:1028–1029
    [Google Scholar]
  18. Timbury M. C., Calder L. 1976; Temperature sensitive mutants of herpes simplex virus type 2: a provisional linkage map based on recombination analysis. Journal of General Virology 30:179–186
    [Google Scholar]
  19. Weissbach A., Hong S-C. L., Aucker J., Miller R. 1973; Characterization of herpes simplex virus induced deoxyribonucleic acid polymerase. Journal of Biological Chemistry 248:6270–6277
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-57-2-297
Loading
/content/journal/jgv/10.1099/0022-1317-57-2-297
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