1887

Abstract

Herpesvirus ribonucleotide reductases, essential for the synthesis of viral DNA, are composed of two non-identical subunits, termed R1 and R2. The U28 ORF from human herpesvirus-7 has been classified, by sequence comparisons, as a homologue of the R1 subunit from ribonucleotide reductase but no R2 ORF is present. Detailed analysis of the U28 amino acid sequence indicated that a number of essential R1 catalytic residues are absent. Cloning and expression of the U28 protein in and its subsequent characterization in subunit interaction and enzyme activity assays confirmed that it is not a functional equivalent of a herpesvirus R1. In the absence of the R2 gene, we propose that the R1 ORF has evolved a distinct, as yet unidentified, function not only in human herpesvirus-7 but also in other human betaherpesviruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-10-2713
1999-10-01
2020-11-30
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/10/0802713a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-10-2713&mimeType=html&fmt=ahah

References

  1. Bonneau A. M., Kibler P., White P., Bousquet C., Dansereau N., Cordingley M. G.. 1996; Resistance of herpes simplex virus type 1 to peptidomimetic ribonucleotide reductase inhibitors: selection and characterization of mutant isolates. Journal of Virology70:787–793
    [Google Scholar]
  2. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchinson C. A., Kouzarides T., Martignetti J. A., Preddie E., Satchwell S. C., Tomlinson P., Weston K. M., Barrell B. G.. 1990; Analysis of the protein coding content of the sequence of human cytomegalovirus strain AD169. Current Topics in Microbiology and Immunology154:125–169
    [Google Scholar]
  3. Conner J., Furlong J., Murray J., Meighan M., Cross A., Marsden H., Clements J. B.. 1993; Herpes simplex virus type 1 ribonucleotide reductase large subunit: regions of the protein essential for subunit interaction and dimerisation. Biochemistry32:13673–13680
    [Google Scholar]
  4. Conner J., Marsden H., Clements J. B.. 1994; Ribonucleotide reductase of herpesviruses. Reviews in Medical Virology4:25–34
    [Google Scholar]
  5. Conner J., Murray J., Cross A., Clements J. B., Marsden H.. 1995; Intracellular localization of herpes simplex virus type 1 ribonucleotide reductase during infection of cultured cells. Virology213:615–623
    [Google Scholar]
  6. Ekberg M., Sahlin M., Eriksson M., Sjoberg B. M.. 1996; Two conserved tyrosine residues in protein R1 participate in an intermolecular electron transfer in ribonucleotide reductase. Journal of Biological Chemistry271:20655–20659
    [Google Scholar]
  7. Ekberg M., Potsch S., Sandin E., Thunnissen M., Nordlund P., Sahlin M., Sjoberg B. M.. 1998; Preserved catalytic activity in an engineered ribonucleotide reductase R2 protein with a nonphysiological radical transfer pathway. Journal of Biological Chemistry273:21003–21008
    [Google Scholar]
  8. Fontecave M.. 1998; Ribonucleotide reductases and radical reactions. Cellular and Molecular Life Sciences54:684–695
    [Google Scholar]
  9. Gompels U. A., Nicholas J., Lawrence G., Jones M., Thomson B. J., Martin M. E. D., Efstathiou M., Craxton M., Macaulay H. A.. 1995; The DNA sequence of human herpesvirus-6: structure, coding content and genome evolution. Virology209:29–51
    [Google Scholar]
  10. Jong A. Y., Yu K., Zhou B., Frgala T., Reynolds C. P., Yen Y.. 1998; A simple and sensitive ribonucleotide reductase assay. Journal of Biomedical Science5:62–68
    [Google Scholar]
  11. Lankinen H., McLauchlan J., Weir M., Furlong J., Conner J., McGarrity A., Mistry A., Clements J. B., Marsden H. S.. 1991; Purification and characterization of the herpes simplex virus type 1 ribonucleotide reductase small subunit following expression in Escherichia coli. Journal of General Virology72:1383–1392
    [Google Scholar]
  12. Licht S., Gerfen G. J., Stubbe J.. 1996; Thiyl radicals in ribonucleotide reductases. Science271:477–481
    [Google Scholar]
  13. Liuzzi M., Deziel R., Moss N., Beaulieu P., Bonneau A. M., Bousquet C., Chafouleas J. G., Garneau M., Jaramillo J., Krogsrud R. L., Lagace L., McCollum R. S., Nawoot S., Guidon Y.. 1994; A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature372:695–698
    [Google Scholar]
  14. Logan D. T., Andersson J., Sjoberg B. M., Nordlund P.. 1999; A glycyl radical site in the crystal structure of a class III ribonucleotide reductase. Science283:1499–1504
    [Google Scholar]
  15. Megaw A. G., Rapaport D., Avidor B., Frenkel N., Davison A.. 1998; The DNA sequence of the RK strain of human herpesvirus 7. Virology244:119–132
    [Google Scholar]
  16. Nicholas J.. 1996; Determination and analysis of the complete nucleotide sequence of human herpesvirus 7. Journal of Virology70:5975–5989
    [Google Scholar]
  17. Reichard P.. 1993; From RNA to DNA, why so many ribonucleotide reductases?. Science260:1773–1777
    [Google Scholar]
  18. Smith C. C., Peng T., Kulka M., Aurelian L.. 1998; The PK domain of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is required for immediate-early gene expression and virus growth. Journal of Virology72:9131–9141
    [Google Scholar]
  19. Stubbe J., Riggs-Gelasco P.. 1998; Harnessing free radicals: formation and function of the tyrosyl radical in ribonucleotide reductase. Trends in Biochemical Sciences23:438–443
    [Google Scholar]
  20. Willoughby K., Bennett M., Williams R. A., McCracken C., Gaskell R. M.. 1997; Sequences of the ribonucleotide reductase-encoding genes of felid herpesvirus 1 and molecular phylogenetic analysis. Virus Genes15:203–218
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-10-2713
Loading
/content/journal/jgv/10.1099/0022-1317-80-10-2713
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