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. 1992 Aug 15;89(16):7310–7314. doi: 10.1073/pnas.89.16.7310

The UL13 gene of herpes simplex virus 1 encodes the functions for posttranslational processing associated with phosphorylation of the regulatory protein alpha 22.

F C Purves 1, B Roizman 1
PMCID: PMC49699  PMID: 1323829

Abstract

The herpes simplex virus 1 genome was shown to encode two genes, US3 and UL13, exhibiting amino acid sequence motifs common to protein kinases. Elsewhere this laboratory reported that the prominent substrate of the US3 protein kinase is the product of the UL34 gene, an essential nonglycosylated membrane protein. In the absence of the US3 kinase, the UL34 protein remains unphosphorylated but forms a complex with four proteins that become phosphorylated uniquely when UL34 is not. To investigate the role of UL13 protein in this process, recombinant viruses lacking UL13 or both UL13 and US3 were constructed. We report that UL13 is dispensable for viral replication in cell culture and is not involved in the processing of UL34 or of associated phosphoproteins. UL13 is, however, responsible for the posttranslational processing associated with phosphorylation of infected-cell protein 22, the product of the alpha 22 gene. This gene was previously reported to play a regulatory role in selected cell lines. UL13 appears to be either a protein kinase or a phosphotransferase and its major substrate is the alpha 22 protein.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackermann M., Braun D. K., Pereira L., Roizman B. Characterization of herpes simplex virus 1 alpha proteins 0, 4, and 27 with monoclonal antibodies. J Virol. 1984 Oct;52(1):108–118. doi: 10.1128/jvi.52.1.108-118.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ackermann M., Sarmiento M., Roizman B. Application of antibody to synthetic peptides for characterization of the intact and truncated alpha 22 protein specified by herpes simplex virus 1 and the R325 alpha 22- deletion mutant. J Virol. 1985 Oct;56(1):207–215. doi: 10.1128/jvi.56.1.207-215.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  4. Banks L. M., Halliburton I. W., Purifoy D. J., Killington R. A., Powell K. L. Studies on the herpes simplex virus alkaline nuclease: detection of type-common and type-specific epitopes on the enzyme. J Gen Virol. 1985 Jan;66(Pt 1):1–14. doi: 10.1099/0022-1317-66-1-1. [DOI] [PubMed] [Google Scholar]
  5. Barker D. E., Roizman B. The unique sequence of the herpes simplex virus 1 L component contains an additional translated open reading frame designated UL49.5. J Virol. 1992 Jan;66(1):562–566. doi: 10.1128/jvi.66.1.562-566.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Batterson W., Furlong D., Roizman B. Molecular genetics of herpes simplex virus. VIII. further characterization of a temperature-sensitive mutant defective in release of viral DNA and in other stages of the viral reproductive cycle. J Virol. 1983 Jan;45(1):397–407. doi: 10.1128/jvi.45.1.397-407.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chee M. S., Lawrence G. L., Barrell B. G. Alpha-, beta- and gammaherpesviruses encode a putative phosphotransferase. J Gen Virol. 1989 May;70(Pt 5):1151–1160. doi: 10.1099/0022-1317-70-5-1151. [DOI] [PubMed] [Google Scholar]
  9. Chou J., Roizman B. The terminal a sequence of the herpes simplex virus genome contains the promoter of a gene located in the repeat sequences of the L component. J Virol. 1986 Feb;57(2):629–637. doi: 10.1128/jvi.57.2.629-637.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cunningham C., Davison A. J., Dolan A., Frame M. C., McGeoch D. J., Meredith D. M., Moss H. W., Orr A. C. The UL13 virion protein of herpes simplex virus type 1 is phosphorylated by a novel virus-induced protein kinase. J Gen Virol. 1992 Feb;73(Pt 2):303–311. doi: 10.1099/0022-1317-73-2-303. [DOI] [PubMed] [Google Scholar]
  11. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  12. Frame M. C., Purves F. C., McGeoch D. J., Marsden H. S., Leader D. P. Identification of the herpes simplex virus protein kinase as the product of viral gene US3. J Gen Virol. 1987 Oct;68(Pt 10):2699–2704. doi: 10.1099/0022-1317-68-10-2699. [DOI] [PubMed] [Google Scholar]
  13. Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lawrence G. L., Chee M., Craxton M. A., Gompels U. A., Honess R. W., Barrell B. G. Human herpesvirus 6 is closely related to human cytomegalovirus. J Virol. 1990 Jan;64(1):287–299. doi: 10.1128/jvi.64.1.287-299.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liu F. Y., Roizman B. The promoter, transcriptional unit, and coding sequence of herpes simplex virus 1 family 35 proteins are contained within and in frame with the UL26 open reading frame. J Virol. 1991 Jan;65(1):206–212. doi: 10.1128/jvi.65.1.206-212.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Longnecker R., Roizman B. Clustering of genes dispensable for growth in culture in the S component of the HSV-1 genome. Science. 1987 May 1;236(4801):573–576. doi: 10.1126/science.3033823. [DOI] [PubMed] [Google Scholar]
  17. Marsden H. S., Stow N. D., Preston V. G., Timbury M. C., Wilkie N. M. Physical mapping of herpes simplex virus-induced polypeptides. J Virol. 1978 Nov;28(2):624–642. doi: 10.1128/jvi.28.2.624-642.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
  19. McGeoch D. J., Davison A. J. Alphaherpesviruses possess a gene homologous to the protein kinase gene family of eukaryotes and retroviruses. Nucleic Acids Res. 1986 Feb 25;14(4):1765–1777. doi: 10.1093/nar/14.4.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McGeoch D. J., Dolan A., Donald S., Rixon F. J. Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. J Mol Biol. 1985 Jan 5;181(1):1–13. doi: 10.1016/0022-2836(85)90320-1. [DOI] [PubMed] [Google Scholar]
  21. Pereira L., Wolff M. H., Fenwick M., Roizman B. Regulation of herpesvirus macromolecular synthesis. V. Properties of alpha polypeptides made in HSV-1 and HSV-2 infected cells. Virology. 1977 Apr;77(2):733–749. doi: 10.1016/0042-6822(77)90495-0. [DOI] [PubMed] [Google Scholar]
  22. Post L. E., Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. Cell. 1981 May;24(2):555–565. doi: 10.1016/0092-8674(81)90346-9. [DOI] [PubMed] [Google Scholar]
  23. Post L. E., Roizman B. A generalized technique for deletion of specific genes in large genomes: alpha gene 22 of herpes simplex virus 1 is not essential for growth. Cell. 1981 Jul;25(1):227–232. doi: 10.1016/0092-8674(81)90247-6. [DOI] [PubMed] [Google Scholar]
  24. Purves F. C., Katan M., Leader D. P. Complete purification of the pseudorabies virus protein kinase. Eur J Biochem. 1987 Sep 15;167(3):507–512. doi: 10.1111/j.1432-1033.1987.tb13366.x. [DOI] [PubMed] [Google Scholar]
  25. Purves F. C., Katan M., Stevely W. S., Leader D. P. Characteristics of the induction of a new protein kinase in cells infected with herpesviruses. J Gen Virol. 1986 Jun;67(Pt 6):1049–1057. doi: 10.1099/0022-1317-67-6-1049. [DOI] [PubMed] [Google Scholar]
  26. Purves F. C., Longnecker R. M., Leader D. P., Roizman B. Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture. J Virol. 1987 Sep;61(9):2896–2901. doi: 10.1128/jvi.61.9.2896-2901.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Purves F. C., Spector D., Roizman B. The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene. J Virol. 1991 Nov;65(11):5757–5764. doi: 10.1128/jvi.65.11.5757-5764.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Purves F. C., Spector D., Roizman B. UL34, the target of the herpes simplex virus U(S)3 protein kinase, is a membrane protein which in its unphosphorylated state associates with novel phosphoproteins. J Virol. 1992 Jul;66(7):4295–4303. doi: 10.1128/jvi.66.7.4295-4303.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Roller R. J., Roizman B. Herpes simplex virus 1 RNA-binding protein US11 negatively regulates the accumulation of a truncated viral mRNA. J Virol. 1991 Nov;65(11):5873–5879. doi: 10.1128/jvi.65.11.5873-5879.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sears A. E., Halliburton I. W., Meignier B., Silver S., Roizman B. Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice. J Virol. 1985 Aug;55(2):338–346. doi: 10.1128/jvi.55.2.338-346.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  32. Walboomers J. M., Schegget J. T. A new method for the isolation of herpes simplex virus type 2 DNA. Virology. 1976 Oct 1;74(1):256–258. doi: 10.1016/0042-6822(76)90151-3. [DOI] [PubMed] [Google Scholar]
  33. Weller S. K., Seghatoleslami M. R., Shao L., Rowse D., Carmichael E. P. The herpes simplex virus type 1 alkaline nuclease is not essential for viral DNA synthesis: isolation and characterization of a lacZ insertion mutant. J Gen Virol. 1990 Dec;71(Pt 12):2941–2952. doi: 10.1099/0022-1317-71-12-2941. [DOI] [PubMed] [Google Scholar]
  34. Wilcox K. W., Kohn A., Sklyanskaya E., Roizman B. Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA. J Virol. 1980 Jan;33(1):167–182. doi: 10.1128/jvi.33.1.167-182.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]

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