Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1988 Jan 25;16(2):555–570. doi: 10.1093/nar/16.2.555

Association of herpes simplex virus regulatory protein ICP4 with sequences spanning the ICP4 gene transcription initiation site.

S W Faber 1, K W Wilcox 1
PMCID: PMC334678  PMID: 2829130

Abstract

The HSV gene encoding ICP4 is negatively regulated and the HSV gene encoding thymidine kinase is positively regulated by ICP4 in vivo. We report that ICP4 is a component of a stable complex that contains protein and a sequence of approximately 28 nucleotides that span the ICP4 gene transcription initiation site. The association of ICP4 with DNA sequences between positions -103 and +32 relative to the ICP4 mRNA start site was demonstrated by DNA binding immunoassays. DNase footprinting revealed that nucleotides between positions -8 and +20 are protected by ICP4. In contrast, binding of ICP4 to sequences flanking the mRNA start site in the thymidine kinase gene was not observed. Models for ICP4-mediated positive or negative regulation of HSV gene transcription are discussed.

Full text

PDF
556

Images in this article

559Image
on p.559
561Image
on p.561
562Image
on p.562
564Image
on p.564

Selected References

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

  1. 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]
  2. Beard P., Faber S., Wilcox K. W., Pizer L. I. Herpes simplex virus immediate early infected-cell polypeptide 4 binds to DNA and promotes transcription. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4016–4020. doi: 10.1073/pnas.83.11.4016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell M. E., Palfreyman J. W., Preston C. M. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J Mol Biol. 1984 Nov 25;180(1):1–19. doi: 10.1016/0022-2836(84)90427-3. [DOI] [PubMed] [Google Scholar]
  4. Coen D. M., Weinheimer S. P., McKnight S. L. A genetic approach to promoter recognition during trans induction of viral gene expression. Science. 1986 Oct 3;234(4772):53–59. doi: 10.1126/science.3018926. [DOI] [PubMed] [Google Scholar]
  5. Cordingley M. G., Campbell M. E., Preston C. M. Functional analysis of a herpes simplex virus type 1 promoter: identification of far-upstream regulatory sequences. Nucleic Acids Res. 1983 Apr 25;11(8):2347–2365. doi: 10.1093/nar/11.8.2347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dalrymple M. A., McGeoch D. J., Davison A. J., Preston C. M. DNA sequence of the herpes simplex virus type 1 gene whose product is responsible for transcriptional activation of immediate early promoters. Nucleic Acids Res. 1985 Nov 11;13(21):7865–7879. doi: 10.1093/nar/13.21.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeLuca N. A., Courtney M. A., Schaffer P. A. Temperature-sensitive mutants in herpes simplex virus type 1 ICP4 permissive for early gene expression. J Virol. 1984 Dec;52(3):767–776. doi: 10.1128/jvi.52.3.767-776.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DeLuca N. A., Schaffer P. A. Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4. Mol Cell Biol. 1985 Aug;5(8):1997–2008. doi: 10.1128/mcb.5.8.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dixon R. A., Schaffer P. A. Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP175. J Virol. 1980 Oct;36(1):189–203. doi: 10.1128/jvi.36.1.189-203.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eisenberg S. P., Coen D. M., McKnight S. L. Promoter domains required for expression of plasmid-borne copies of the herpes simplex virus thymidine kinase gene in virus-infected mouse fibroblasts and microinjected frog oocytes. Mol Cell Biol. 1985 Aug;5(8):1940–1947. doi: 10.1128/mcb.5.8.1940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. ElKareh A., Murphy A. J., Fichter T., Efstratiadis A., Silverstein S. "Transactivation" control signals in the promoter of the herpesvirus thymidine kinase gene. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1002–1006. doi: 10.1073/pnas.82.4.1002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Everett R. D. A detailed analysis of an HSV-1 early promoter: sequences involved in trans-activation by viral immediate-early gene products are not early-gene specific. Nucleic Acids Res. 1984 Apr 11;12(7):3037–3056. doi: 10.1093/nar/12.7.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Everett R. D. Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. EMBO J. 1984 Dec 20;3(13):3135–3141. doi: 10.1002/j.1460-2075.1984.tb02270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Faber S. W., Wilcox K. W. Association of the herpes simplex virus regulatory protein ICP4 with specific nucleotide sequences in DNA. Nucleic Acids Res. 1986 Aug 11;14(15):6067–6083. doi: 10.1093/nar/14.15.6067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Faber S. W., Wilcox K. W. Characterization of a herpes simplex virus regulatory protein: aggregation and phosphorylation of a temperature-sensitive variant of ICP 4. Arch Virol. 1986;91(3-4):297–312. doi: 10.1007/BF01314289. [DOI] [PubMed] [Google Scholar]
  16. Galas D. J., Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978 Sep;5(9):3157–3170. doi: 10.1093/nar/5.9.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gelman I. H., Silverstein S. Co-ordinate regulation of herpes simplex virus gene expression is mediated by the functional interaction of two immediate early gene products. J Mol Biol. 1986 Oct 5;191(3):395–409. doi: 10.1016/0022-2836(86)90135-x. [DOI] [PubMed] [Google Scholar]
  18. Godowski P. J., Knipe D. M. Transcriptional control of herpesvirus gene expression: gene functions required for positive and negative regulation. Proc Natl Acad Sci U S A. 1986 Jan;83(2):256–260. doi: 10.1073/pnas.83.2.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goldin A. L., Sandri-Goldin R. M., Levine M., Glorioso J. C. Cloning of herpes simplex virus type 1 sequences representing the whole genome. J Virol. 1981 Apr;38(1):50–58. doi: 10.1128/jvi.38.1.50-58.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Graves B. J., Johnson P. F., McKnight S. L. Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell. 1986 Feb 28;44(4):565–576. doi: 10.1016/0092-8674(86)90266-7. [DOI] [PubMed] [Google Scholar]
  21. Honess R. W., Roizman B. Proteins specified by herpes simplex virus. XI. Identification and relative molar rates of synthesis of structural and nonstructural herpes virus polypeptides in the infected cell. J Virol. 1973 Dec;12(6):1347–1365. doi: 10.1128/jvi.12.6.1347-1365.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  24. Jones K. A., Tjian R. Sp1 binds to promoter sequences and activates herpes simplex virus 'immediate-early' gene transcription in vitro. Nature. 1985 Sep 12;317(6033):179–182. doi: 10.1038/317179a0. [DOI] [PubMed] [Google Scholar]
  25. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  26. Kristie T. M., Roizman B. Alpha 4, the major regulatory protein of herpes simplex virus type 1, is stably and specifically associated with promoter-regulatory domains of alpha genes and of selected other viral genes. Proc Natl Acad Sci U S A. 1986 May;83(10):3218–3222. doi: 10.1073/pnas.83.10.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kristie T. M., Roizman B. DNA-binding site of major regulatory protein alpha 4 specifically associated with promoter-regulatory domains of alpha genes of herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4700–4704. doi: 10.1073/pnas.83.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kristie T. M., Roizman B. Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus 1 alpha genes. Proc Natl Acad Sci U S A. 1987 Jan;84(1):71–75. doi: 10.1073/pnas.84.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kristie T. M., Roizman B. Separation of sequences defining basal expression from those conferring alpha gene recognition within the regulatory domains of herpes simplex virus 1 alpha genes. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4065–4069. doi: 10.1073/pnas.81.13.4065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lang J. C., Spandidos D. A., Wilkie N. M. Transcriptional regulation of a herpes simplex virus immediate early gene is mediated through an enhancer-type sequence. EMBO J. 1984 Feb;3(2):389–395. doi: 10.1002/j.1460-2075.1984.tb01817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mackem S., Roizman B. Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4917–4921. doi: 10.1073/pnas.79.16.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mackem S., Roizman B. Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase genes. J Virol. 1982 Dec;44(3):939–949. doi: 10.1128/jvi.44.3.939-949.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  34. McGeoch D. J., Dolan A., Donald S., Brauer D. H. Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Res. 1986 Feb 25;14(4):1727–1745. doi: 10.1093/nar/14.4.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. McKay R. D. Binding of a simian virus 40 T antigen-related protein to DNA. J Mol Biol. 1981 Jan 25;145(3):471–488. doi: 10.1016/0022-2836(81)90540-4. [DOI] [PubMed] [Google Scholar]
  36. McKnight S. L. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Res. 1980 Dec 20;8(24):5949–5964. doi: 10.1093/nar/8.24.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Metzler D. W., Wilcox K. W. Isolation of herpes simplex virus regulatory protein ICP4 as a homodimeric complex. J Virol. 1985 Aug;55(2):329–337. doi: 10.1128/jvi.55.2.329-337.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Muller M. T. Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site. J Virol. 1987 Mar;61(3):858–865. doi: 10.1128/jvi.61.3.858-865.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. O'Hare P., Hayward G. S. Comparison of upstream sequence requirements for positive and negative regulation of a herpes simplex virus immediate-early gene by three virus-encoded trans-acting factors. J Virol. 1987 Jan;61(1):190–199. doi: 10.1128/jvi.61.1.190-199.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. O'Hare P., Hayward G. S. Evidence for a direct role for both the 175,000- and 110,000-molecular-weight immediate-early proteins of herpes simplex virus in the transactivation of delayed-early promoters. J Virol. 1985 Mar;53(3):751–760. doi: 10.1128/jvi.53.3.751-760.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. O'Hare P., Hayward G. S. Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation. J Virol. 1985 Dec;56(3):723–733. doi: 10.1128/jvi.56.3.723-733.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pellett P. E., McKnight J. L., Jenkins F. J., Roizman B. Nucleotide sequence and predicted amino acid sequence of a protein encoded in a small herpes simplex virus DNA fragment capable of trans-inducing alpha genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870–5874. doi: 10.1073/pnas.82.17.5870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Pizer L. I., Tedder D. G., Betz J. L., Wilcox K. W., Beard P. Regulation of transcription in vitro from herpes simplex virus genes. J Virol. 1986 Dec;60(3):950–959. doi: 10.1128/jvi.60.3.950-959.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Preston C. M. Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. J Virol. 1979 Jan;29(1):275–284. doi: 10.1128/jvi.29.1.275-284.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Preston C. M., Cordingley M. G., Stow N. D. Analysis of DNA sequences which regulate the transcription of a herpes simplex virus immediate early gene. J Virol. 1984 Jun;50(3):708–716. doi: 10.1128/jvi.50.3.708-716.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Quinlan M. P., Knipe D. M. Stimulation of expression of a herpes simplex virus DNA-binding protein by two viral functions. Mol Cell Biol. 1985 May;5(5):957–963. doi: 10.1128/mcb.5.5.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Read G. S., Frenkel N. Herpes simplex virus mutants defective in the virion-associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of alpha (immediate early) viral polypeptides. J Virol. 1983 May;46(2):498–512. doi: 10.1128/jvi.46.2.498-512.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stow N. D., McMonagle E. C. Characterization of the TRS/IRS origin of DNA replication of herpes simplex virus type 1. Virology. 1983 Oct 30;130(2):427–438. doi: 10.1016/0042-6822(83)90097-1. [DOI] [PubMed] [Google Scholar]
  49. Watson R. J., Clements J. B. A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature. 1980 May 29;285(5763):329–330. doi: 10.1038/285329a0. [DOI] [PubMed] [Google Scholar]
  50. Watson R. J., Preston C. M., Clements J. B. Separation and characterization of herpes simplex virus type 1 immediate-early mRNA's. J Virol. 1979 Jul;31(1):42–52. doi: 10.1128/jvi.31.1.42-52.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Weinheimer S. P., McKnight S. L. Transcriptional and post-transcriptional controls establish the cascade of herpes simplex virus protein synthesis. J Mol Biol. 1987 Jun 20;195(4):819–833. doi: 10.1016/0022-2836(87)90487-6. [DOI] [PubMed] [Google Scholar]
  52. Whitton J. L., Rixon F. J., Easton A. J., Clements J. B. Immediate-early mRNA-2 of herpes simplex viruses types 1 and 2 is unspliced: conserved sequences around the 5' and 3' termini correspond to transcription regulatory signals. Nucleic Acids Res. 1983 Sep 24;11(18):6271–6287. doi: 10.1093/nar/11.18.6271. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES