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. 1985 May;54(2):414–421. doi: 10.1128/jvi.54.2.414-421.1985

Cells that constitutively express the herpes simplex virus immediate-early protein ICP4 allow efficient activation of viral delayed-early genes in trans.

R H Persson, S Bacchetti, J R Smiley
PMCID: PMC254812  PMID: 2985804

Abstract

To study the role of herpes simplex virus type 1 immediate-early proteins in the transcriptional activation of herpes simplex virus genes, we isolated stably transformed cells expressing herpes simplex virus type 1 ICP4, an immediate-early protein known from previous studies to be necessary for delayed-early and late transcription. These cells efficiently expressed six delayed-early herpes simplex virus genes introduced by viral superinfection, in the absence of de novo viral protein synthesis. In contrast, the delayed-early gene encoding alkaline exonuclease and the late gene encoding the capsid protein VP5 were expressed at much lower levels. Expression of a second late gene, that for glycoprotein C, was undetectable under the same experimental conditions. These results suggest that many, but not all, delayed-early genes are efficiently activated by ICP4; in addition, they demonstrate that although the late gene for VP5 is detectably activated by ICP4, its full expression requires additional factors.

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Selected References

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

  1. Anderson K. P., Costa R. H., Holland L. E., Wagner E. K. Characterization of herpes simplex virus type 1 RNA present in the absence of de novo protein synthesis. J Virol. 1980 Apr;34(1):9–27. doi: 10.1128/jvi.34.1.9-27.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bacchetti S., Evelegh M. J., Muirhead B., Sartori C. S., Huszar D. Immunological characterization of herpes simplex virus type 1 and 2 polypeptide(s) involved in viral ribonucleotide reductase activity. J Virol. 1984 Feb;49(2):591–593. doi: 10.1128/jvi.49.2.591-593.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balachandran N., Harnish D., Rawls W. E., Bacchetti S. Glycoproteins of herpes simplex virus type 2 as defined by monoclonal antibodies. J Virol. 1982 Oct;44(1):344–355. doi: 10.1128/jvi.44.1.344-355.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
  5. Banks L., Purifoy D. J., Hurst P. F., Killington R. A., Powell K. L. Herpes simplex virus non-structural proteins. IV. Purification of the virus-induced deoxyribonuclease and characterization of the enzyme using monoclonal antibodies. J Gen Virol. 1983 Oct;64(Pt 10):2249–2260. doi: 10.1099/0022-1317-64-10-2249. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  8. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  9. Campione-Piccardo J., Rawls W. E. Inability to rescue viral genes from human cells biochemically transformed by herpes simplex virus type 2 DNA. Can J Microbiol. 1981 Oct;27(10):1123–1128. doi: 10.1139/m81-175. [DOI] [PubMed] [Google Scholar]
  10. Clements J. B., McLauchlan J., McGeoch D. J. Orientation of herpes simplex virus type 1 immediate early mRNA's. Nucleic Acids Res. 1979 Sep 11;7(1):77–91. doi: 10.1093/nar/7.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Costa R. H., Cohen G., Eisenberg R., Long D., Wagner E. Direct demonstration that the abundant 6-kilobase herpes simplex virus type 1 mRNA mapping between 0.23 and 0.27 map units encodes the major capsid protein VP5. J Virol. 1984 Jan;49(1):287–292. doi: 10.1128/jvi.49.1.287-292.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Costa R. H., Draper K. G., Banks L., Powell K. L., Cohen G., Eisenberg R., Wagner E. K. High-resolution characterization of herpes simplex virus type 1 transcripts encoding alkaline exonuclease and a 50,000-dalton protein tentatively identified as a capsid protein. J Virol. 1983 Dec;48(3):591–603. doi: 10.1128/jvi.48.3.591-603.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Costanzo F., Campadelli-Fiume G., Foa-Tomasi L., Cassai E. Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. J Virol. 1977 Mar;21(3):996–1001. doi: 10.1128/jvi.21.3.996-1001.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Everett R. D. DNA sequence elements required for regulated expression of the HSV-1 glycoprotein D gene lie within 83 bp of the RNA capsites. Nucleic Acids Res. 1983 Oct 11;11(19):6647–6666. doi: 10.1093/nar/11.19.6647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  18. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  19. Green M. R., Treisman R., Maniatis T. Transcriptional activation of cloned human beta-globin genes by viral immediate-early gene products. Cell. 1983 Nov;35(1):137–148. doi: 10.1016/0092-8674(83)90216-7. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Imperiale M. J., Feldman L. T., Nevins J. R. Activation of gene expression by adenovirus and herpesvirus regulatory genes acting in trans and by a cis-acting adenovirus enhancer element. Cell. 1983 Nov;35(1):127–136. doi: 10.1016/0092-8674(83)90215-5. [DOI] [PubMed] [Google Scholar]
  22. Kahn M., Kolter R., Thomas C., Figurski D., Meyer R., Remaut E., Helinski D. R. Plasmid cloning vehicles derived from plasmids ColE1, F, R6K, and RK2. Methods Enzymol. 1979;68:268–280. doi: 10.1016/0076-6879(79)68019-9. [DOI] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Lee G. T., Para M. F., Spear P. G. Location of the structural genes for glycoproteins gD and gE and for other polypeptides in the S component of herpes simplex virus type 1 DNA. J Virol. 1982 Jul;43(1):41–49. doi: 10.1128/jvi.43.1.41-49.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Leung W. C., Dimock K., Smiley J. R., Bacchetti S. Herpes simplex virus thymidine kinase transcripts are absent from both nucleus and cytoplasm during infection in the presence of cycloheximide. J Virol. 1980 Nov;36(2):361–365. doi: 10.1128/jvi.36.2.361-365.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Mackem S., Roizman B. Regulation of herpesvirus macromolecular synthesis: transcription-initiation sites and domains of alpha genes. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7122–7126. doi: 10.1073/pnas.77.12.7122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Palfreyman J. W., Maclean J. B., Messeder E., Sheppard R. C. Successful use of oligopeptides as immunogens in the preparation of antisera to immediate-early gene products of herpes simplex virus type 1. J Gen Virol. 1984 May;65(Pt 5):865–874. doi: 10.1099/0022-1317-65-5-865. [DOI] [PubMed] [Google Scholar]
  31. Pellicer A., Robins D., Wold B., Sweet R., Jackson J., Lowy I., Roberts J. M., Sim G. K., Silverstein S., Axel R. Altering genotype and phenotype by DNA-mediated gene transfer. Science. 1980 Sep 19;209(4463):1414–1422. doi: 10.1126/science.7414320. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Powell K. L., Purifoy D. J. DNA-binding proteins of cells infected by herpes simplex virus type 1 and type 2. Intervirology. 1976;7(4-5):225–239. doi: 10.1159/000149955. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Rixon F. J., Clements J. B. Detailed structural analysis of two spliced HSV-1 immediate-early mRNAs. Nucleic Acids Res. 1982 Apr 10;10(7):2241–2256. doi: 10.1093/nar/10.7.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Roberts J. M., Axel R. Gene amplification and gene correction in somatic cells. Cell. 1982 May;29(1):109–119. doi: 10.1016/0092-8674(82)90095-2. [DOI] [PubMed] [Google Scholar]
  37. Sandri-Goldin R. M., Goldin A. L., Holland L. E., Glorioso J. C., Levine M. Expression of herpes simplex virus beta and gamma genes integrated in mammalian cells and their induction by an alpha gene product. Mol Cell Biol. 1983 Nov;3(11):2028–2044. doi: 10.1128/mcb.3.11.2028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Showalter S. D., Zweig M., Hampar B. Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP 4. Infect Immun. 1981 Dec;34(3):684–692. doi: 10.1128/iai.34.3.684-692.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Smiley J. R., Swan H., Pater M. M., Pater A., Halpern M. E. Positive control of the herpes simplex virus thymidine kinase gene requires upstream DNA sequences. J Virol. 1983 Aug;47(2):301–310. doi: 10.1128/jvi.47.2.301-310.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Watson R. J., Vande Woude G. F. DNA sequence of an immediate-early gene (IEmRNA-5) of herpes simplex virus type I. Nucleic Acids Res. 1982 Feb 11;10(3):979–991. doi: 10.1093/nar/10.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. 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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