1887

Abstract

Vmw175, the product of herpes simplex virus type 1 immediate early (IE) gene 3, is essential for viral replication. It is required for the activation of transcription from both early and late gene promoters and also for the repression of IE gene expression. Vmwl75 is able to bind specifically to certain DNA sequences, some of which (including that at the cap site of IE gene 3) contain the consensus sequence ATCGTC. The presence of this sequence at the cap site has been correlated with the ability of Vmw175 to autoregulate its own promoter. This report describes the characterization of five viruses with temperature-sensitive (ts) lesions in Vmwl75. Four of these mutants express Vmw175 which is ts in its ability to bind to DNA and to autoregulate IE-3 gene expression in the infected cell. Although Vmw175 produced by the remaining mutant, ts1225, fails to autoregulate IE-3 expression at the non-permissive temperature (NPT) its DNA-binding properties are indistinguishable from those of the wild-type protein. This suggests that the ability of Vmw175 to bind to the IE-3 cap site (as measured ) is insufficient for autoregulation (). All five newly characterized ts mutants are partially permissive for early gene transcription at the NPT, although Vmw175 expressed by four of them is unable to bind to the IE-3 cap site sequence at elevated temperatures. This suggests that binding to one class of recognition sequences by Vmw175, as measured is not absolutely required for the activation of early gene promoters during virus infection. The lesions in these five ts mutants lie in the carboxy- terminal third of the polypeptide; three of the mutations (those in tsl219, ts1221 and ts1225) were identified by DNA sequence analysis and were found to affect amino acid residues that are conserved in the homologous proteins from varicella-zoster virus and pseudorabies virus.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-71-4-851
1990-04-01
2024-03-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/71/4/JV0710040851.html?itemId=/content/journal/jgv/10.1099/0022-1317-71-4-851&mimeType=html&fmt=ahah

References

  1. Abmayr S. M., Feldman L. D., Roeder R. G. 1985; In vitro stimulation of specific RNA polymerase II mediated transcription by the pseudorabies virus immediate early protein. Cell 43:821–829
    [Google Scholar]
  2. Beard P., Faber S., Wilcox K. W., Pizer L. I. 1986; Herpes simplex virus immediate early infected cell polypeptide 4 binds to DNA and promotes transcription. Proceedings of the National Academy of Sciences, U.S.A 83:4016–4020
    [Google Scholar]
  3. Campbell M. E. M., Palfreyman J. W., Preston C. M. 1984; Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. Journal of Molecular Biology 180:1–19
    [Google Scholar]
  4. Costanzo F., Campadelli-Fiume G., Foa-Tomasi L., Cassai E. 1977; Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. Journal of Virology 21:996–1001
    [Google Scholar]
  5. Cromlish W. A., Abmayr S. M., Workman J. L., Horikoshi M., Roeder R. G. 1989; Transcriptionally active immediate-early protein of pseudorabies virus binds to specific sites on class II gene promoters. Journal of Virology 63:1869–1876
    [Google Scholar]
  6. Davison M.-J., Preston V. G., Mcgeoch D. J. 1984; Determination of the sequence alteration in the DNA of the herpes simplex virus type 1 temperature-sensitive mutant ts K. Journal of General Virology 65:859–863
    [Google Scholar]
  7. Deluca N. A., Schaffer P. A. 1987; Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense polypeptides. Nucleic Acids Research 15:4491–4511
    [Google Scholar]
  8. Deluca N. A., Schaffer P. A. 1988; Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP4. Journal of Virology 62:732–743
    [Google Scholar]
  9. Deluca N. A., Courtney M. A., Schaffer P. A. 1984; Temperature-sensitive mutants in herpes simplex virus type 1 ICP4 permissive for early gene expression. Journal of Virology 52:767–776
    [Google Scholar]
  10. Dignam J. D., Lebovitz R. M., Roeder R. G. 1983; Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Research 11:1475–1489
    [Google Scholar]
  11. Everett R. D. 1984; Transactivation of transcription by herpes virus products; requirements for two HSV-1 immediate early polypeptides for maximum activity. EMBO Journal 3:3135–3141
    [Google Scholar]
  12. Everett R. D. 1986; The products of herpes simplex virus type 1 (HSV-1) immediate early genes 1, 2 and 3 can activate gene expression in trans . Journal of General Virology 67:2507–2513
    [Google Scholar]
  13. Everett R. D. 1987; The regulation of transcription of viral and cellular genes by herpesvirus immediate-early gene products. Anticancer Research 7:589–604
    [Google Scholar]
  14. Everett R. D. 1989; Construction and characterization of herpes simplex virus type 1 mutants with defined lesions in immediate early gene 1. Journal of General Virology 70:1185–1202
    [Google Scholar]
  15. Faber S. W., Wilcox K. W. 1986; Association of the herpes simplex virus regulatory protein ICP4 with specific nucleotide sequences in DNA. Nucleic Acids Research 14:6067–6083
    [Google Scholar]
  16. Garner M. M., Revzin A. 1981; A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Research 9:3047–3060
    [Google Scholar]
  17. Gerster T., Roeder R. G. 1988; A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins. Proceedings of the National Academy of Sciences, U.S.A 85:6347–6351
    [Google Scholar]
  18. Heilbronn R., zur Hausen H. 1989; A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome. Journal of Virology 63:3683–3692
    [Google Scholar]
  19. Kattar-Cooley P., Wilcox K. W. 1989; Characterization of the DNA-binding properties of herpes simplex virus regulatory protein ICP4. Journal of Virology 63:696–704
    [Google Scholar]
  20. Mcgeoch D. J., Dolan A., Donald S., Brauer D. H. K. 1986; Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Research 14:1727–1764
    [Google Scholar]
  21. Mcgeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., Mcnab D., Perry L. J., Scott J. E., Taylor P. 1988a; The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:1531–1574
    [Google Scholar]
  22. Mcgeoch D. J., Dalrymple M. A., Dolan A., Mcnab D., Perry L. J., Taylor P., Challberg M. D. 1988b; Structures of herpes simplex type 1 genes required for replication of virus DNA. Journal of Virology 62:444–453
    [Google Scholar]
  23. Mcknight J. L., Kristie T. M., Roizman B. 1987; Binding of the virion protein mediating gene induction in herpes simplex virus type 1 infected cells to its cis site requires cellular proteins. Proceedings of the National Academy of Sciences, U.S.A 84:7061–7065
    [Google Scholar]
  24. Marsden H. S., Crombie I. K., Subak-Sharpe J. H. 1976; Control of protein synthesis in herpesvirus-infected cells: analysis of the polypeptides induced by wild type and sixteen temperature- sensitive mutants of HSV strain 17. Journal of General Virology 31:347–372
    [Google Scholar]
  25. Marsden H. S., Stow N. D., Preston V. G., Timbury M. C., Wilkie N. M. 1978; Physical mapping of herpes simplex virus-induced polypeptides. Journal of Virology 28:624–642
    [Google Scholar]
  26. Michael N., Spector D., Mavromara-Nazos P., Kristie T. M., Roizman B. 1988; The DNA-binding properties of the major regulatory protein α4 of herpes simplex virus. Science 239:1531–1534
    [Google Scholar]
  27. Muller M. T. 1987; Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site. Journal of Virology 61:858–865
    [Google Scholar]
  28. O’Hare P., Goding C. R. 1988; Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell 52:435–445
    [Google Scholar]
  29. O’Hare P., Hayward G. S. 1985; Evidence for a direct role for both the 175,000- and 110,000-molecular-weight immediate-early proteins of herpes virus in the transactivation of delayed-early promoters. Journal of Virology 53:751–760
    [Google Scholar]
  30. Paterson T. 1989 A mutational analysis of the structure and function of the herpes simplex virus immediate early protein Vmwl75 Ph.D. thesis University of Glasgow:
    [Google Scholar]
  31. Paterson T., Everett R. D. 1988a; Mutational dissection of the HSV-1 immediate-early protein Vmwl75 involved in transcriptional transactivation and repression. Virology 166:186–196
    [Google Scholar]
  32. Paterson T., Everett R. D. 1988b; The regions of the herpes simplex virus type 1 immediate early protein Vmwl75 required for site specific DNA binding closely correspond to those involved in transcriptional regulation. Nucleic Acids Research 16:11005–11025
    [Google Scholar]
  33. Preston C. M. 1979a; Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature- sensitive mutant tsK. Journal of Virology 29:275–284
    [Google Scholar]
  34. Preston C. M. 1979b; Abnormal properties of an immediate early polypeptide in cells infected with the herpes simplex virus type 1 mutant tsK. Journal of Virology 32:357–369
    [Google Scholar]
  35. Preston C. M., Frame M. C., Campbell M. E. M. 1988; A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory sequence. Cell 52:425–434
    [Google Scholar]
  36. Preston V. G. 1981; Fine-structure mapping of herpes simplex virus type 1 temperature-sensitive mutations within the short repeat region of the genome. Journal of Virology 39:150–161
    [Google Scholar]
  37. Roberts M. S., Boundy A., O’Hare P., Pizzorno M. C., Ciufo D. M., Hayward G. S. 1988; Direct correlation between a negative autoregulatory response element at the cap site of the herpes simplex virus type 1 IE 175 (a4) promoter and a specific binding site for the IE175 (ICP4) protein. Journal of Virology 62:4307–4320
    [Google Scholar]
  38. Russell J., Stow E. C., Stow N. D., Preston C. M. 1987; Abnormal forms of the herpes simplex virus immediate early polypeptide Vmwl75 induce the cellular stress response. Journal of General Virology 68:2397–2406
    [Google Scholar]
  39. Sacks W. R., Greene C. C., Aschman D. P., Schaffer P. A. 1985; Herpes simplex virus type 1ICP27 is an essential regulatory protein. Journal of Virology 55:796–805
    [Google Scholar]
  40. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A 74:5463–5467
    [Google Scholar]
  41. Sanger F., Coulson A. R., Barrell B. G., Smith A. J. H., Roe B. A. 1980; Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. Journal of Molecular Biology 143:161–178
    [Google Scholar]
  42. Sekulovich R. E., Leary K., Sandri-Goldin R. M. 1988; The herpes simplex virus type 1 protein ICP27 can act as a transrepressor or a trans-activator in combination with ICP4 and ICP0. Journal of Virology 62:4510–4522
    [Google Scholar]
  43. Shepard A. A., Imbalzano A. N., Deluca N. A. 1989; Separation of primary structural components conferring autoregulation, transactivation, and DNA-binding properties to the herpes simplex virus transcriptional regulatory protein ICP4. Journal of Virology 63:3714–3728
    [Google Scholar]
  44. Showalter L. D., Zweig M., Hampar B. 1981; Monoclonal antibodies to herpes simplex type 1 proteins including the immediate-early protein ICP4. Infection and Immunity 34:684–692
    [Google Scholar]
  45. Stow N. D., Stow E. C. 1986; Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate-early polypeptide Vmwl 10. Journal of General Virology 67:2571–2585
    [Google Scholar]
  46. Stow N. D., Mcmonagle E. C., Davison A. J. 1983; Fragments from both termini of the herpes simplex virus type 1 genome contain signals required for the encapsidation of viral DNA. Nucleic Acids Research 11:8205–8220
    [Google Scholar]
  47. Tedder D. G., Everett R. D., Wilcox K. W., Beard P., Pizer L. I. 1989; ICP4-binding sites in the promoter and coding regions of the herpes simplex virus gD gene contribute to activation of in vitro transcription by ICP4. Journal of Virology 63:2510–2520
    [Google Scholar]
  48. Vlcek C., Paces V., Schwyzer M. 1989; Nucleotide sequence of the pseudorabies virus immediate early gene, encoding a strong trans-activator protein. Virus Genes 2:335–346
    [Google Scholar]
  49. Wagner E. K. 1985; Individual HSV transcripts: characterisation of specific genes. In The Herpesviruses 3 pp. 45–104 Roizman B. Edited by New York & London: Plenum Press;
    [Google Scholar]
  50. Watson R. J., Clements J. B. 1980; A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature; London: 285329–330
    [Google Scholar]
  51. Workman J. L., Abmayr S. M., Cromlish W. A., Roeder R. G. 1988; Transcriptional regulation by the immediate early protein of pseudorabies virus during in vitro nucleosome assembly. Cell 55:211–219
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-71-4-851
Loading
/content/journal/jgv/10.1099/0022-1317-71-4-851
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