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. 1994 Sep;68(9):5738–5747. doi: 10.1128/jvi.68.9.5738-5747.1994

The herpes simplex virus type 1 major capsid protein (VP5-UL19) promoter contains two cis-acting elements influencing late expression.

C J Huang 1, E K Wagner 1
PMCID: PMC236977  PMID: 8057455

Abstract

The herpes simplex virus type 1 (HSV-1) major capsid protein VP5 gene (UL19) is expressed with beta gamma (gamma 1 [leaky late]) kinetics. We have previously described the construction of recombinant HSV-1 in which the VP5 promoter was engineered to control the expression of the bacterial beta-galactosidase gene as a reporter (C.-J. Huang, S. A. Goodart, M. K. Rice, J. F. Guzowski, and E. K. Wagner, J. Virol. 67:5109-5116, 1993). Here we describe further mutational analysis in recombinant viruses. We have precisely defined the boundaries of the VP5 promoter and identified two regions important for both the level and the kinetics of expression. The 5' boundary was located at -48 relative to the initiation site of transcription by analyzing a series of nested deletions in the upstream sequence, and although a number of cis-acting sites influencing transient expression have been identified upstream of this point, these sites have no role in promoter activity during productive infection. Deletion of an Sp1-binding site located between -48 and the TATA box at -30 greatly reduced VP5 promoter activity late but not early after infection. A cis-acting element whose sequence resembles the human immunodeficiency virus type 1 initiator was located between -2 and +10 in the VP5 sequence by characterizing a series of deletions and site-directed block mutations downstream the TATA box. This element defines the 3' limit of the VP5 promoter, and like the upstream element, disruption of this element also inhibited promoter activity late in the productive cycle.

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Selected References

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

  1. Blair E. D., Wagner E. K. A single regulatory region modulates both cis activation and trans activation of the herpes simplex virus VP5 promoter in transient-expression assays in vivo. J Virol. 1986 Nov;60(2):460–469. doi: 10.1128/jvi.60.2.460-469.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cai W., Schaffer P. A. Herpes simplex virus type 1 ICP0 regulates expression of immediate-early, early, and late genes in productively infected cells. J Virol. 1992 May;66(5):2904–2915. doi: 10.1128/jvi.66.5.2904-2915.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen J., Silverstein S. Herpes simplex viruses with mutations in the gene encoding ICP0 are defective in gene expression. J Virol. 1992 May;66(5):2916–2927. doi: 10.1128/jvi.66.5.2916-2927.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen S., Mills L., Perry P., Riddle S., Wobig R., Lown R., Millette R. L. Transactivation of the major capsid protein gene of herpes simplex virus type 1 requires a cellular transcription factor. J Virol. 1992 Jul;66(7):4304–4314. doi: 10.1128/jvi.66.7.4304-4314.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dennis D., Smiley J. R. Transactivation of a late herpes simplex virus promoter. Mol Cell Biol. 1984 Mar;4(3):544–551. doi: 10.1128/mcb.4.3.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Du H., Roy A. L., Roeder R. G. Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. EMBO J. 1993 Feb;12(2):501–511. doi: 10.1002/j.1460-2075.1993.tb05682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Flanagan W. M., Papavassiliou A. G., Rice M., Hecht L. B., Silverstein S., Wagner E. K. Analysis of the herpes simplex virus type 1 promoter controlling the expression of UL38, a true late gene involved in capsid assembly. J Virol. 1991 Feb;65(2):769–786. doi: 10.1128/jvi.65.2.769-786.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gao M., Knipe D. M. Potential role for herpes simplex virus ICP8 DNA replication protein in stimulation of late gene expression. J Virol. 1991 May;65(5):2666–2675. doi: 10.1128/jvi.65.5.2666-2675.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goodart S. A., Guzowski J. F., Rice M. K., Wagner E. K. Effect of genomic location on expression of beta-galactosidase mRNA controlled by the herpes simplex virus type 1 UL38 promoter. J Virol. 1992 May;66(5):2973–2981. doi: 10.1128/jvi.66.5.2973-2981.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guzowski J. F., Wagner E. K. Mutational analysis of the herpes simplex virus type 1 strict late UL38 promoter/leader reveals two regions critical in transcriptional regulation. J Virol. 1993 Sep;67(9):5098–5108. doi: 10.1128/jvi.67.9.5098-5108.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Homa F. L., Glorioso J. C., Levine M. A specific 15-bp TATA box promoter element is required for expression of a herpes simplex virus type 1 late gene. Genes Dev. 1988 Jan;2(1):40–53. doi: 10.1101/gad.2.1.40. [DOI] [PubMed] [Google Scholar]
  13. Homa F. L., Otal T. M., Glorioso J. C., Levine M. Transcriptional control signals of a herpes simplex virus type 1 late (gamma 2) gene lie within bases -34 to +124 relative to the 5' terminus of the mRNA. Mol Cell Biol. 1986 Nov;6(11):3652–3666. doi: 10.1128/mcb.6.11.3652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huang C. J., Barrett E. L. Sequence analysis and expression of the Salmonella typhimurium asr operon encoding production of hydrogen sulfide from sulfite. J Bacteriol. 1991 Feb;173(4):1544–1553. doi: 10.1128/jb.173.4.1544-1553.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huang C. J., Goodart S. A., Rice M. K., Guzowski J. F., Wagner E. K. Mutational analysis of sequences downstream of the TATA box of the herpes simplex virus type 1 major capsid protein (VP5/UL19) promoter. J Virol. 1993 Sep;67(9):5109–5116. doi: 10.1128/jvi.67.9.5109-5116.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Imbalzano A. N., DeLuca N. A. Substitution of a TATA box from a herpes simplex virus late gene in the viral thymidine kinase promoter alters ICP4 inducibility but not temporal expression. J Virol. 1992 Sep;66(9):5453–5463. doi: 10.1128/jvi.66.9.5453-5463.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jackson S. P., Tjian R. Purification and analysis of RNA polymerase II transcription factors by using wheat germ agglutinin affinity chromatography. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1781–1785. doi: 10.1073/pnas.86.6.1781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnson P. A., Everett R. D. The control of herpes simplex virus type-1 late gene transcription: a 'TATA-box'/cap site region is sufficient for fully efficient regulated activity. Nucleic Acids Res. 1986 Nov 11;14(21):8247–8264. doi: 10.1093/nar/14.21.8247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Kibler P. K., Duncan J., Keith B. D., Hupel T., Smiley J. R. Regulation of herpes simplex virus true late gene expression: sequences downstream from the US11 TATA box inhibit expression from an unreplicated template. J Virol. 1991 Dec;65(12):6749–6760. doi: 10.1128/jvi.65.12.6749-6760.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Knipe D. M. The role of viral and cellular nuclear proteins in herpes simplex virus replication. Adv Virus Res. 1989;37:85–123. doi: 10.1016/s0065-3527(08)60833-7. [DOI] [PubMed] [Google Scholar]
  22. Lee K. A., Green M. R. Small-scale preparation of extracts from radiolabeled cells efficient in pre-mRNA splicing. Methods Enzymol. 1990;181:20–30. doi: 10.1016/0076-6879(90)81108-7. [DOI] [PubMed] [Google Scholar]
  23. Lin Y. S., Carey M., Ptashne M., Green M. R. How different eukaryotic transcriptional activators can cooperate promiscuously. Nature. 1990 May 24;345(6273):359–361. doi: 10.1038/345359a0. [DOI] [PubMed] [Google Scholar]
  24. Margolis D. M., Ostrove J. M., Straus S. E. HSV-1 activation of HIV-1 transcription is augmented by a cellular protein that binds near the initiator element. Virology. 1993 Jan;192(1):370–374. doi: 10.1006/viro.1993.1046. [DOI] [PubMed] [Google Scholar]
  25. Margolis D. M., Somasundaran M., Green M. R. Human transcription factor YY1 represses human immunodeficiency virus type 1 transcription and virion production. J Virol. 1994 Feb;68(2):905–910. doi: 10.1128/jvi.68.2.905-910.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mavromara-Nazos P., Roizman B. Activation of herpes simplex virus 1 gamma 2 genes by viral DNA replication. Virology. 1987 Dec;161(2):593–598. doi: 10.1016/0042-6822(87)90156-5. [DOI] [PubMed] [Google Scholar]
  27. Mavromara-Nazos P., Roizman B. Delineation of regulatory domains of early (beta) and late (gamma 2) genes by construction of chimeric genes expressed in herpes simplex virus 1 genomes. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4071–4075. doi: 10.1073/pnas.86.11.4071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mavromara-Nazos P., Silver S., Hubenthal-Voss J., McKnight J. L., Roizman B. Regulation of herpes simplex virus 1 genes: alpha gene sequence requirements for transient induction of indicator genes regulated by beta or late (gamma 2) promoters. Virology. 1986 Mar;149(2):152–164. doi: 10.1016/0042-6822(86)90117-0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. McKnight S. L. Constitutive transcriptional control signals of the herpes simplex virus tk gene. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):945–958. doi: 10.1101/sqb.1983.047.01.108. [DOI] [PubMed] [Google Scholar]
  31. McKnight S. L. Functional relationships between transcriptional control signals of the thymidine kinase gene of herpes simplex virus. Cell. 1982 Dec;31(2 Pt 1):355–365. doi: 10.1016/0092-8674(82)90129-5. [DOI] [PubMed] [Google Scholar]
  32. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  33. Mills L. K., Shi Y., Millette R. L. YY1 is the cellular factor shown previously to bind to regulatory regions of several leaky-late (beta gamma, gamma 1) genes of herpes simplex virus type 1. J Virol. 1994 Feb;68(2):1234–1238. doi: 10.1128/jvi.68.2.1234-1238.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mondésert G., Kédinger C. Cooperation between upstream and downstream elements of the adenovirus major late promoter for maximal late phase-specific transcription. Nucleic Acids Res. 1991 Jun 25;19(12):3221–3228. doi: 10.1093/nar/19.12.3221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Roy A. L., Meisterernst M., Pognonec P., Roeder R. G. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF. Nature. 1991 Nov 21;354(6350):245–248. doi: 10.1038/354245a0. [DOI] [PubMed] [Google Scholar]
  36. Sethna M., Weir J. P. Mutational analysis of the herpes simplex virus type 1 glycoprotein E promoter. Virology. 1993 Oct;196(2):532–540. doi: 10.1006/viro.1993.1508. [DOI] [PubMed] [Google Scholar]
  37. Shapira M., Homa F. L., Glorioso J. C., Levine M. Regulation of the herpes simplex virus type 1 late (gamma 2) glycoprotein C gene: sequences between base pairs -34 to +29 control transient expression and responsiveness to transactivation by the products of the immediate early (alpha) 4 and 0 genes. Nucleic Acids Res. 1987 Apr 10;15(7):3097–3111. doi: 10.1093/nar/15.7.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Silver S., Roizman B. gamma 2-Thymidine kinase chimeras are identically transcribed but regulated a gamma 2 genes in herpes simplex virus genomes and as beta genes in cell genomes. Mol Cell Biol. 1985 Mar;5(3):518–528. doi: 10.1128/mcb.5.3.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Smiley J. R., Smibert C., Everett R. D. Expression of a cellular gene cloned in herpes simplex virus: rabbit beta-globin is regulated as an early viral gene in infected fibroblasts. J Virol. 1987 Aug;61(8):2368–2377. doi: 10.1128/jvi.61.8.2368-2377.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Steffy K. R., Weir J. P. Mutational analysis of two herpes simplex virus type 1 late promoters. J Virol. 1991 Dec;65(12):6454–6460. doi: 10.1128/jvi.65.12.6454-6460.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Steffy K. R., Weir J. P. Upstream promoter elements of the herpes simplex virus type 1 glycoprotein H gene. J Virol. 1991 Feb;65(2):972–975. doi: 10.1128/jvi.65.2.972-975.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Zhang Y. F., Wagner E. K. The kinetics of expression of individual herpes simplex virus type 1 transcripts. Virus Genes. 1987 Nov;1(1):49–60. doi: 10.1007/BF00125685. [DOI] [PubMed] [Google Scholar]
  44. Zipser D., Lipsich L., Kwoh J. Mapping functional domains in the promoter region of the herpes thymidine kinase gene. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6276–6280. doi: 10.1073/pnas.78.10.6276. [DOI] [PMC free article] [PubMed] [Google Scholar]

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