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. 1997 Sep;71(9):7073–7079. doi: 10.1128/jvi.71.9.7073-7079.1997

Varicella-zoster virus open reading frame 4 encodes an immediate-early protein with posttranscriptional regulatory properties.

P Defechereux 1, S Debrus 1, L Baudoux 1, B Rentier 1, J Piette 1
PMCID: PMC191997  PMID: 9261438

Abstract

Varicella-zoster virus (VZV) encodes four putative immediate-early proteins based on sequence homology with herpes simplex virus type 1: the products of ORF4, -61, -62, and -63. Until now, only two VZV proteins have been described as being truly expressed with immediate-early kinetics (IE62 and IE63). The ORF4-encoded protein can stimulate gene expression either alone or in synergy with the major regulatory protein IE62. Making use of a sequential combination of transcription and protein synthesis inhibitors (actinomycin D and cycloheximide, respectively), we demonstrated the immediate-early nature of the ORF4 gene product, which can thus be named IE4. The fact that IE4 is expressed with kinetics similar to that of IE62 further underlines the possible cooperation between these two VZV proteins in gene expression. Analysis of the IE4-mediated autologous or heterologous viral gene expression at the mRNA levels clearly indicated that IE4 may have several mechanisms of action. Activation of the two VZV genes tested could occur partly by a posttranscriptional mechanism, since increases in chloramphenicol acetyltransferase (CAT) mRNA levels do not account for the stimulation of CAT activity. On the other hand, stimulation of the human immunodeficiency virus type 1 long terminal repeat- or the cytomegalovirus promoter-associated CAT activity is correlated with an increase in the corresponding CAT mRNA.

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Selected References

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  1. Ackermann M., Braun D. K., Pereira L., Roizman B. Characterization of herpes simplex virus 1 alpha proteins 0, 4, and 27 with monoclonal antibodies. J Virol. 1984 Oct;52(1):108–118. doi: 10.1128/jvi.52.1.108-118.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Baudoux L., Defechereux P., Schoonbroodt S., Merville M. P., Rentier B., Piette J. Mutational analysis of varicella-zoster virus major immediate-early protein IE62. Nucleic Acids Res. 1995 Apr 25;23(8):1341–1349. doi: 10.1093/nar/23.8.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Davison A. J., McGeoch D. J. Evolutionary comparisons of the S segments in the genomes of herpes simplex virus type 1 and varicella-zoster virus. J Gen Virol. 1986 Apr;67(Pt 4):597–611. doi: 10.1099/0022-1317-67-4-597. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Debrus S., Sadzot-Delvaux C., Nikkels A. F., Piette J., Rentier B. Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency. J Virol. 1995 May;69(5):3240–3245. doi: 10.1128/jvi.69.5.3240-3245.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Defechereux P., Debrus S., Baudoux L., Schoonbroodt S., Merville M. P., Rentier B., Piette J. Intracellular distribution of the ORF4 gene product of varicella-zoster virus is influenced by the IE62 protein. J Gen Virol. 1996 Jul;77(Pt 7):1505–1513. doi: 10.1099/0022-1317-77-7-1505. [DOI] [PubMed] [Google Scholar]
  11. Defechereux P., Melen L., Baudoux L., Merville-Louis M. P., Rentier B., Piette J. Characterization of the regulatory functions of varicella-zoster virus open reading frame 4 gene product. J Virol. 1993 Jul;67(7):4379–4385. doi: 10.1128/jvi.67.7.4379-4385.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Everett R. D. The regulation of transcription of viral and cellular genes by herpesvirus immediate-early gene products (review). Anticancer Res. 1987 Jul-Aug;7(4A):589–604. [PubMed] [Google Scholar]
  13. Felser J. M., Straus S. E., Ostrove J. M. Varicella-zoster virus complements herpes simplex virus type 1 temperature-sensitive mutants. J Virol. 1987 Jan;61(1):225–228. doi: 10.1128/jvi.61.1.225-228.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Forghani B., Mahalingam R., Vafai A., Hurst J. W., Dupuis K. W. Monoclonal antibody to immediate early protein encoded by varicella-zoster virus gene 62. Virus Res. 1990 Jun;16(2):195–210. doi: 10.1016/0168-1702(90)90023-5. [DOI] [PubMed] [Google Scholar]
  15. Furnari F. B., Adams M. D., Pagano J. S. Regulation of the Epstein-Barr virus DNA polymerase gene. J Virol. 1992 May;66(5):2837–2845. doi: 10.1128/jvi.66.5.2837-2845.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gendelman H. E., Phelps W., Feigenbaum L., Ostrove J. M., Adachi A., Howley P. M., Khoury G., Ginsberg H. S., Martin M. A. Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759–9763. doi: 10.1073/pnas.83.24.9759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Inchauspe G., Nagpal S., Ostrove J. M. Mapping of two varicella-zoster virus-encoded genes that activate the expression of viral early and late genes. Virology. 1989 Dec;173(2):700–709. doi: 10.1016/0042-6822(89)90583-7. [DOI] [PubMed] [Google Scholar]
  19. Inchauspe G., Ostrove J. M. Differential regulation by varicella-zoster virus (VZV) and herpes simplex virus type-1 trans-activating genes. Virology. 1989 Dec;173(2):710–714. doi: 10.1016/0042-6822(89)90584-9. [DOI] [PubMed] [Google Scholar]
  20. Kinchington P. R., Bookey D., Turse S. E. The transcriptional regulatory proteins encoded by varicella-zoster virus open reading frames (ORFs) 4 and 63, but not ORF 61, are associated with purified virus particles. J Virol. 1995 Jul;69(7):4274–4282. doi: 10.1128/jvi.69.7.4274-4282.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kinchington P. R., Hougland J. K., Arvin A. M., Ruyechan W. T., Hay J. The varicella-zoster virus immediate-early protein IE62 is a major component of virus particles. J Virol. 1992 Jan;66(1):359–366. doi: 10.1128/jvi.66.1.359-366.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kinchington P. R., Vergnes J. P., Defechereux P., Piette J., Turse S. E. Transcriptional mapping of the varicella-zoster virus regulatory genes encoding open reading frames 4 and 63. J Virol. 1994 Jun;68(6):3570–3581. doi: 10.1128/jvi.68.6.3570-3581.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kost R. G., Kupinsky H., Straus S. E. Varicella-zoster virus gene 63: transcript mapping and regulatory activity. Virology. 1995 May 10;209(1):218–224. doi: 10.1006/viro.1995.1246. [DOI] [PubMed] [Google Scholar]
  24. Kozak M. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem. 1991 Oct 25;266(30):19867–19870. [PubMed] [Google Scholar]
  25. 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]
  26. McLauchlan J., Phelan A., Loney C., Sandri-Goldin R. M., Clements J. B. Herpes simplex virus IE63 acts at the posttranscriptional level to stimulate viral mRNA 3' processing. J Virol. 1992 Dec;66(12):6939–6945. doi: 10.1128/jvi.66.12.6939-6945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mears W. E., Rice S. A. The RGG box motif of the herpes simplex virus ICP27 protein mediates an RNA-binding activity and determines in vivo methylation. J Virol. 1996 Nov;70(11):7445–7453. doi: 10.1128/jvi.70.11.7445-7453.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moriuchi H., Moriuchi M., Smith H. A., Cohen J. I. Varicella-zoster virus open reading frame 4 protein is functionally distinct from and does not complement its herpes simplex virus type 1 homolog, ICP27. J Virol. 1994 Mar;68(3):1987–1992. doi: 10.1128/jvi.68.3.1987-1992.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Moriuchi H., Moriuchi M., Straus S. E., Cohen J. I. Varicella-zoster virus (VZV) open reading frame 61 protein transactivates VZV gene promoters and enhances the infectivity of VZV DNA. J Virol. 1993 Jul;67(7):4290–4295. doi: 10.1128/jvi.67.7.4290-4295.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Moriuchi M., Moriuchi H., Debrus S., Piette J., Cohen J. I. The acidic amino-terminal region of varicella-zoster virus open reading frame 4 protein is required for transactivation and can functionally replace the corresponding region of herpes simplex virus ICP27. Virology. 1995 Apr 1;208(1):376–382. doi: 10.1006/viro.1995.1164. [DOI] [PubMed] [Google Scholar]
  32. Moriuchi M., Moriuchi H., Straus S. E., Cohen J. I. Varicella-zoster virus (VZV) virion-associated transactivator open reading frame 62 protein enhances the infectivity of VZV DNA. Virology. 1994 Apr;200(1):297–300. doi: 10.1006/viro.1994.1190. [DOI] [PubMed] [Google Scholar]
  33. Nagpal S., Ostrove J. M. Characterization of a potent varicella-zoster virus-encoded trans-repressor. J Virol. 1991 Oct;65(10):5289–5296. doi: 10.1128/jvi.65.10.5289-5296.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pasleau F., Tocci M. J., Leung F., Kopchick J. J. Growth hormone gene expression in eukaryotic cells directed by the Rous sarcoma virus long terminal repeat or cytomegalovirus immediate-early promoter. Gene. 1985;38(1-3):227–232. doi: 10.1016/0378-1119(85)90221-5. [DOI] [PubMed] [Google Scholar]
  35. Pelletier J., Sonenberg N. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency. Cell. 1985 Mar;40(3):515–526. doi: 10.1016/0092-8674(85)90200-4. [DOI] [PubMed] [Google Scholar]
  36. Perera L. P., Kaushal S., Kinchington P. R., Mosca J. D., Hayward G. S., Straus S. E. Varicella-zoster virus open reading frame 4 encodes a transcriptional activator that is functionally distinct from that of herpes simplex virus homology ICP27. J Virol. 1994 Apr;68(4):2468–2477. doi: 10.1128/jvi.68.4.2468-2477.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Perera L. P., Mosca J. D., Ruyechan W. T., Hay J. Regulation of varicella-zoster virus gene expression in human T lymphocytes. J Virol. 1992 Sep;66(9):5298–5304. doi: 10.1128/jvi.66.9.5298-5304.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rice S. A., Knipe D. M. Gene-specific transactivation by herpes simplex virus type 1 alpha protein ICP27. J Virol. 1988 Oct;62(10):3814–3823. doi: 10.1128/jvi.62.10.3814-3823.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rice S. A., Knipe D. M. Genetic evidence for two distinct transactivation functions of the herpes simplex virus alpha protein ICP27. J Virol. 1990 Apr;64(4):1704–1715. doi: 10.1128/jvi.64.4.1704-1715.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sacks W. R., Greene C. C., Aschman D. P., Schaffer P. A. Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol. 1985 Sep;55(3):796–805. doi: 10.1128/jvi.55.3.796-805.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Saito M., Haruyama C., Ohba H., Makino S., Matumoto M. Recovery of cell-free varicella virus from Vero cells. Arch Virol. 1981;68(1):59–63. doi: 10.1007/BF01315168. [DOI] [PubMed] [Google Scholar]
  42. Sandri-Goldin R. M., Mendoza G. E. A herpesvirus regulatory protein appears to act post-transcriptionally by affecting mRNA processing. Genes Dev. 1992 May;6(5):848–863. doi: 10.1101/gad.6.5.848. [DOI] [PubMed] [Google Scholar]
  43. Smith I. L., Hardwicke M. A., Sandri-Goldin R. M. Evidence that the herpes simplex virus immediate early protein ICP27 acts post-transcriptionally during infection to regulate gene expression. Virology. 1992 Jan;186(1):74–86. doi: 10.1016/0042-6822(92)90062-t. [DOI] [PubMed] [Google Scholar]

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