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. 1994 Aug;68(8):4898–4909. doi: 10.1128/jvi.68.8.4898-4909.1994

Protein and DNA elements involved in transactivation of the promoter of the bovine herpesvirus (BHV) 1 IE-1 transcription unit by the BHV alpha gene trans-inducing factor.

V Misra 1, A C Bratanich 1, D Carpenter 1, P O'Hare 1
PMCID: PMC236430  PMID: 8035488

Abstract

In herpes simplex virus (HSV)-infected cells, the transcription of immediate-early (alpha) genes is regulated by a virion component, the alpha gene trans-inducing factor (alpha TIF). This protein forms a complex with cellular factors and TAATGARAT motifs present in one or more copies in the promoters of all alpha genes. We have characterized the bovine herpesvirus 1 (BHV-1) homolog of this protein. Like its HSV counterpart, the BHV alpha TIF was synthesized in the later stages of infection and could be demonstrated to be a component of purified virions. In transient expression assays, BHV alpha TIF was a strong transactivator and stimulated the activity of IE-1, the major BHV-1 alpha gene promoter, with an efficiency comparable to that of HSV alpha TIF. This stimulation was largely dependent on a TAATGAGCT sequence present in a single copy in IE-1, and BHV alpha TIF, in conjunction with cellular factors, formed a complex with oligonucleotides containing this sequence. Despite these similarities between the two alpha TIFs, our preliminary observations suggest that the proteins may activate transcription by different mechanisms. Although BHV alpha TIF strongly transactivated IE-1, it differed from its HSV counterpart in that the carboxyl terminus of BHV alpha TIF, when fused to the DNA-binding domain of GAL4, was a relatively poor stimulator of a promoter containing GAL4-binding sites. Also unlike HSV alpha TIF, removal of the carboxyl terminus of BHV alpha TIF reduced but did not eliminate the ability of the protein to transactivate IE-1. These results are discussed in view of the structural similarities and differences among the alpha TIFs of alphaherpes-viruses.

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Selected References

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

  1. Ace C. I., Dalrymple M. A., Ramsay F. H., Preston V. G., Preston C. M. Mutational analysis of the herpes simplex virus type 1 trans-inducing factor Vmw65. J Gen Virol. 1988 Oct;69(Pt 10):2595–2605. doi: 10.1099/0022-1317-69-10-2595. [DOI] [PubMed] [Google Scholar]
  2. 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]
  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. Carpenter D. E., Misra V. Sequences of the bovine herpesvirus 1 homologue of herpes simplex virus type-1 alpha-trans-inducing factor (UL48). Gene. 1992 Oct 1;119(2):259–263. doi: 10.1016/0378-1119(92)90280-3. [DOI] [PubMed] [Google Scholar]
  5. Carpenter D. E., Misra V. The most abundant protein in bovine herpes 1 virions is a homologue of herpes simplex virus type 1 UL47. J Gen Virol. 1991 Dec;72(Pt 12):3077–3084. doi: 10.1099/0022-1317-72-12-3077. [DOI] [PubMed] [Google Scholar]
  6. Caughman G. B., Staczek J., O'Callaghan D. J. Equine herpesvirus type 1 infected cell polypeptides: evidence for immediate early/early/late regulation of viral gene expression. Virology. 1985 Aug;145(1):49–61. doi: 10.1016/0042-6822(85)90200-4. [DOI] [PubMed] [Google Scholar]
  7. Choy B., Green M. R. Eukaryotic activators function during multiple steps of preinitiation complex assembly. Nature. 1993 Dec 9;366(6455):531–536. doi: 10.1038/366531a0. [DOI] [PubMed] [Google Scholar]
  8. Cousens D. J., Greaves R., Goding C. R., O'Hare P. The C-terminal 79 amino acids of the herpes simplex virus regulatory protein, Vmw65, efficiently activate transcription in yeast and mammalian cells in chimeric DNA-binding proteins. EMBO J. 1989 Aug;8(8):2337–2342. doi: 10.1002/j.1460-2075.1989.tb08361.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cress A., Triezenberg S. J. Nucleotide and deduced amino acid sequences of the gene encoding virion protein 16 of herpes simplex virus type 2. Gene. 1991 Jul 22;103(2):235–238. doi: 10.1016/0378-1119(91)90278-j. [DOI] [PubMed] [Google Scholar]
  10. Cress W. D., Triezenberg S. J. Critical structural elements of the VP16 transcriptional activation domain. Science. 1991 Jan 4;251(4989):87–90. doi: 10.1126/science.1846049. [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. Gerster T., Roeder R. G. A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6347–6351. doi: 10.1073/pnas.85.17.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goodrich J. A., Hoey T., Thut C. J., Admon A., Tjian R. Drosophila TAFII40 interacts with both a VP16 activation domain and the basal transcription factor TFIIB. Cell. 1993 Nov 5;75(3):519–530. doi: 10.1016/0092-8674(93)90386-5. [DOI] [PubMed] [Google Scholar]
  14. Greaves R. F., O'Hare P. Sequence, function, and regulation of the Vmw65 gene of herpes simplex virus type 2. J Virol. 1991 Dec;65(12):6705–6713. doi: 10.1128/jvi.65.12.6705-6713.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Greaves R. F., O'Hare P. Structural requirements in the herpes simplex virus type 1 transactivator Vmw65 for interaction with the cellular octamer-binding protein and target TAATGARAT sequences. J Virol. 1990 Jun;64(6):2716–2724. doi: 10.1128/jvi.64.6.2716-2724.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Greaves R., O'Hare P. Separation of requirements for protein-DNA complex assembly from those for functional activity in the herpes simplex virus regulatory protein Vmw65. J Virol. 1989 Apr;63(4):1641–1650. doi: 10.1128/jvi.63.4.1641-1650.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haigh A., Greaves R., O'Hare P. Interference with the assembly of a virus-host transcription complex by peptide competition. Nature. 1990 Mar 15;344(6263):257–259. doi: 10.1038/344257a0. [DOI] [PubMed] [Google Scholar]
  18. Hayes S., O'Hare P. Mapping of a major surface-exposed site in herpes simplex virus protein Vmw65 to a region of direct interaction in a transcription complex assembly. J Virol. 1993 Feb;67(2):852–862. doi: 10.1128/jvi.67.2.852-862.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ihara S., Feldman L., Watanabe S., Ben-Porat T. Characterization of the immediate-early functions of pseudorabies virus. Virology. 1983 Dec;131(2):437–454. doi: 10.1016/0042-6822(83)90510-x. [DOI] [PubMed] [Google Scholar]
  20. Katan M., Haigh A., Verrijzer C. P., van der Vliet P. C., O'Hare P. Characterization of a cellular factor which interacts functionally with Oct-1 in the assembly of a multicomponent transcription complex. Nucleic Acids Res. 1990 Dec 11;18(23):6871–6880. doi: 10.1093/nar/18.23.6871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kristie T. M., LeBowitz J. H., Sharp P. A. The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein. EMBO J. 1989 Dec 20;8(13):4229–4238. doi: 10.1002/j.1460-2075.1989.tb08608.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Lewis J. B., Thompson Y. G., Caughman G. B. Transcriptional control of the equine herpesvirus 1 immediate early gene. Virology. 1993 Dec;197(2):788–792. doi: 10.1006/viro.1993.1658. [DOI] [PubMed] [Google Scholar]
  24. Liao S. M., Taylor I. C., Kingston R. E., Young R. A. RNA polymerase II carboxy-terminal domain contributes to the response to multiple acidic activators in vitro. Genes Dev. 1991 Dec;5(12B):2431–2440. doi: 10.1101/gad.5.12b.2431. [DOI] [PubMed] [Google Scholar]
  25. Lin Y. S., Green M. R. Mechanism of action of an acidic transcriptional activator in vitro. Cell. 1991 Mar 8;64(5):971–981. doi: 10.1016/0092-8674(91)90321-o. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Marsden H. S., Campbell M. E., Haarr L., Frame M. C., Parris D. S., Murphy M., Hope R. G., Muller M. T., Preston C. M. The 65,000-Mr DNA-binding and virion trans-inducing proteins of herpes simplex virus type 1. J Virol. 1987 Aug;61(8):2428–2437. doi: 10.1128/jvi.61.8.2428-2437.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McKee T. A., Disney G. H., Everett R. D., Preston C. M. Control of expression of the varicella-zoster virus major immediate early gene. J Gen Virol. 1990 Apr;71(Pt 4):897–906. doi: 10.1099/0022-1317-71-4-897. [DOI] [PubMed] [Google Scholar]
  29. McKnight J. L., Kristie T. M., Roizman B. Binding of the virion protein mediating alpha gene induction in herpes simplex virus 1-infected cells to its cis site requires cellular proteins. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7061–7065. doi: 10.1073/pnas.84.20.7061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Misra V., Blewett E. L. Construction of herpes simplex viruses that are pseudodiploid for the glycoprotein B gene: a strategy for studying the function of an essential herpesvirus gene. J Gen Virol. 1991 Feb;72(Pt 2):385–392. doi: 10.1099/0022-1317-72-2-385. [DOI] [PubMed] [Google Scholar]
  31. Misra V., Blumenthal R. M., Babiuk L. A. Proteins Specified by bovine herpesvirus 1 (infectious bovine rhinotracheitis virus). J Virol. 1981 Nov;40(2):367–378. doi: 10.1128/jvi.40.2.367-378.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Misra V., Gilchrist J. E., Weinmaster G., Qualtiere L., Van den Hurk S., Babiuk L. A. Herpesvirus-induced "early" glycoprotein: characterization and possible role in immune cytolysis. J Virol. 1982 Sep;43(3):1046–1054. doi: 10.1128/jvi.43.3.1046-1054.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Moriuchi H., Moriuchi M., Straus S. E., Cohen J. I. Varicella-zoster virus open reading frame 10 protein, the herpes simplex virus VP16 homolog, transactivates herpesvirus immediate-early gene promoters. J Virol. 1993 May;67(5):2739–2746. doi: 10.1128/jvi.67.5.2739-2746.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nelson R., Adachi A. M., Chisholm H., Misra V. Temperature-sensitive mutants of bovine herpesvirus type 1: mutants which make unaltered levels of 'early' glycoproteins but fail to synthesize a 'late' glycoprotein. J Gen Virol. 1989 Jan;70(Pt 1):125–132. doi: 10.1099/0022-1317-70-1-125. [DOI] [PubMed] [Google Scholar]
  35. O'Hare P., Goding C. R., Haigh A. Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression. EMBO J. 1988 Dec 20;7(13):4231–4238. doi: 10.1002/j.1460-2075.1988.tb03320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. O'Hare P., Goding C. R. Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell. 1988 Feb 12;52(3):435–445. doi: 10.1016/s0092-8674(88)80036-9. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. Preston C. M., Frame M. C., Campbell M. E. A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory DNA sequence. Cell. 1988 Feb 12;52(3):425–434. doi: 10.1016/s0092-8674(88)80035-7. [DOI] [PubMed] [Google Scholar]
  40. Purewal A. S., Allsopp R., Riggio M., Telford E. A., Azam S., Davison A. J., Edington N. Equid herpesviruses 1 and 4 encode functional homologs of the herpes simplex virus type 1 virion transactivator protein, VP16. Virology. 1994 Jan;198(1):385–389. doi: 10.1006/viro.1994.1047. [DOI] [PubMed] [Google Scholar]
  41. Purewal A. S., Smallwood A. V., Kaushal A., Adegboye D., Edington N. Identification and control of the cis-acting elements of the immediate early gene of equid herpesvirus type 1. J Gen Virol. 1992 Mar;73(Pt 3):513–519. doi: 10.1099/0022-1317-73-3-513. [DOI] [PubMed] [Google Scholar]
  42. Regier J. L., Shen F., Triezenberg S. J. Pattern of aromatic and hydrophobic amino acids critical for one of two subdomains of the VP16 transcriptional activator. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):883–887. doi: 10.1073/pnas.90.3.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sadowski I., Bell B., Broad P., Hollis M. GAL4 fusion vectors for expression in yeast or mammalian cells. Gene. 1992 Sep 1;118(1):137–141. doi: 10.1016/0378-1119(92)90261-m. [DOI] [PubMed] [Google Scholar]
  44. Sadowski I., Ma J., Triezenberg S., Ptashne M. GAL4-VP16 is an unusually potent transcriptional activator. Nature. 1988 Oct 6;335(6190):563–564. doi: 10.1038/335563a0. [DOI] [PubMed] [Google Scholar]
  45. Schwyzer M., Vlcek C., Menekse O., Fraefel C., Paces V. Promoter, spliced leader, and coding sequence for BICP4, the largest of the immediate-early proteins of bovine herpesvirus 1. Virology. 1993 Nov;197(1):349–357. doi: 10.1006/viro.1993.1596. [DOI] [PubMed] [Google Scholar]
  46. Stern S., Herr W. The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain. Genes Dev. 1991 Dec;5(12B):2555–2566. doi: 10.1101/gad.5.12b.2555. [DOI] [PubMed] [Google Scholar]
  47. Stern S., Tanaka M., Herr W. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989 Oct 19;341(6243):624–630. doi: 10.1038/341624a0. [DOI] [PubMed] [Google Scholar]
  48. Tasset D., Tora L., Fromental C., Scheer E., Chambon P. Distinct classes of transcriptional activating domains function by different mechanisms. Cell. 1990 Sep 21;62(6):1177–1187. doi: 10.1016/0092-8674(90)90394-t. [DOI] [PubMed] [Google Scholar]
  49. Triezenberg S. J., LaMarco K. L., McKnight S. L. Evidence of DNA: protein interactions that mediate HSV-1 immediate early gene activation by VP16. Genes Dev. 1988 Jun;2(6):730–742. doi: 10.1101/gad.2.6.730. [DOI] [PubMed] [Google Scholar]
  50. Wagner W. N., Bogdan J., Haines D., Townsend H. G., Misra V. Detection of equine herpesvirus and differentiation of equine herpesvirus type 1 from type 4 by the polymerase chain reaction. Can J Microbiol. 1992 Nov;38(11):1193–1196. doi: 10.1139/m92-196. [DOI] [PubMed] [Google Scholar]
  51. Walker S., Greaves R., O'Hare P. Transcriptional activation by the acidic domain of Vmw65 requires the integrity of the domain and involves additional determinants distinct from those necessary for TFIIB binding. Mol Cell Biol. 1993 Sep;13(9):5233–5244. doi: 10.1128/mcb.13.9.5233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Werstuck G., Capone J. P. Mutational analysis of the herpes simplex virus trans-inducing factor Vmw65. Gene. 1989 Feb 20;75(2):213–224. doi: 10.1016/0378-1119(89)90267-9. [DOI] [PubMed] [Google Scholar]
  53. Whitton J. L., Clements J. B. Replication origins and a sequence involved in coordinate induction of the immediate-early gene family are conserved in an intergenic region of herpes simplex virus. Nucleic Acids Res. 1984 Feb 24;12(4):2061–2079. doi: 10.1093/nar/12.4.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Wilson A. C., LaMarco K., Peterson M. G., Herr W. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Cell. 1993 Jul 16;74(1):115–125. doi: 10.1016/0092-8674(93)90299-6. [DOI] [PubMed] [Google Scholar]
  55. Wirth U. V., Fraefel C., Vogt B., Vlcek C., Paces V., Schwyzer M. Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3' coterminal and encode a putative zinc finger transactivator protein. J Virol. 1992 May;66(5):2763–2772. doi: 10.1128/jvi.66.5.2763-2772.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wirth U. V., Vogt B., Schwyzer M. The three major immediate-early transcripts of bovine herpesvirus 1 arise from two divergent and spliced transcription units. J Virol. 1991 Jan;65(1):195–205. doi: 10.1128/jvi.65.1.195-205.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wu C. Two protein-binding sites in chromatin implicated in the activation of heat-shock genes. Nature. 1984 May 17;309(5965):229–234. doi: 10.1038/309229a0. [DOI] [PubMed] [Google Scholar]
  58. Xiao P., Capone J. P. A cellular factor binds to the herpes simplex virus type 1 transactivator Vmw65 and is required for Vmw65-dependent protein-DNA complex assembly with Oct-1. Mol Cell Biol. 1990 Sep;10(9):4974–4977. doi: 10.1128/mcb.10.9.4974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. apRhys C. M., Ciufo D. M., O'Neill E. A., Kelly T. J., Hayward G. S. Overlapping octamer and TAATGARAT motifs in the VF65-response elements in herpes simplex virus immediate-early promoters represent independent binding sites for cellular nuclear factor III. J Virol. 1989 Jun;63(6):2798–2812. doi: 10.1128/jvi.63.6.2798-2812.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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