Abstract
Varicella-zoster virus (VZV) gene 63 encodes a protein with a predicted molecular mass of 30.5 kDa which has amino acid similarities with the immediate-early (IE) protein 22 (ICP-22) of herpes simplex virus type 1. In order to study the expression of this protein during lytic and latent infection, gene 63 was cloned in frame and downstream from the glutathione-S-transferase gene, expressed as a fusion protein, and purified. In VZV-infected Vero cells, antibodies directed against this protein detect two polypeptides of 45 and 38 kDa which are localized both in the cytoplasm and in the nucleus. Using a sequential combination of transcription and protein synthesis inhibitors (actinomycin D and cycloheximide, respectively), we demonstrated the immediate-early nature of this protein, which can thus be named IE63. Using a rat model of VZV latency, we showed that IE63 is heavily expressed, essentially in neurons, during latency. IE63 can also be detected in the skin of patients showing early herpes zoster symptoms.
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- 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]
- Cabirac G. F., Mahalingam R., Wellish M., Gilden D. H. Trans-activation of viral tk promoters by proteins encoded by varicella zoster virus open reading frames 61 and 62. Virus Res. 1990 Jan;15(1):57–68. doi: 10.1016/0168-1702(90)90013-2. [DOI] [PubMed] [Google Scholar]
- 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]
- Croen K. D., Ostrove J. M., Dragovic L. J., Straus S. E. Patterns of gene expression and sites of latency in human nerve ganglia are different for varicella-zoster and herpes simplex viruses. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9773–9777. doi: 10.1073/pnas.85.24.9773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Davison A. J., Wilkie N. M. Location and orientation of homologous sequences in the genomes of five herpesviruses. J Gen Virol. 1983 Sep;64(Pt 9):1927–1942. doi: 10.1099/0022-1317-64-9-1927. [DOI] [PubMed] [Google Scholar]
- 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]
- Disney G. H., McKee T. A., Preston C. M., Everett R. D. The product of varicella-zoster virus gene 62 autoregulates its own promoter. J Gen Virol. 1990 Dec;71(Pt 12):2999–3003. doi: 10.1099/0022-1317-71-12-2999. [DOI] [PubMed] [Google Scholar]
- 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]
- Felser J. M., Kinchington P. R., Inchauspe G., Straus S. E., Ostrove J. M. Cell lines containing varicella-zoster virus open reading frame 62 and expressing the "IE" 175 protein complement ICP4 mutants of herpes simplex virus type 1. J Virol. 1988 Jun;62(6):2076–2082. doi: 10.1128/jvi.62.6.2076-2082.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Hyman R. W., Ecker J. R., Tenser R. B. Varicella-zoster virus RNA in human trigeminal ganglia. Lancet. 1983 Oct 8;2(8354):814–816. doi: 10.1016/s0140-6736(83)90736-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Jackers P., Defechereux P., Baudoux L., Lambert C., Massaer M., Merville-Louis M. P., Rentier B., Piette J. Characterization of regulatory functions of the varicella-zoster virus gene 63-encoded protein. J Virol. 1992 Jun;66(6):3899–3903. doi: 10.1128/jvi.66.6.3899-3903.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lopetegui P., Campo-Vera H., Yamanishi K. Varicella-zoster virus (VZV)-specific polypeptides detected in cells treated with metabolic inhibitors. Microbiol Immunol. 1985;29(6):569–575. doi: 10.1111/j.1348-0421.1985.tb00860.x. [DOI] [PubMed] [Google Scholar]
- Merville-Louis M. P., Sadzot-Delvaux C., Delrée P., Piette J., Moonen G., Rentier B. Varicella-zoster virus infection of adult rat sensory neurons in vitro. J Virol. 1989 Jul;63(7):3155–3160. doi: 10.1128/jvi.63.7.3155-3160.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Moriuchi H., Moriuchi M., Smith H. A., Straus S. E., Cohen J. I. Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0. J Virol. 1992 Dec;66(12):7303–7308. doi: 10.1128/jvi.66.12.7303-7308.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Nikkels A. F., Debrus S., Sadzot-Delvaux C., Piette J., Delvenne P., Rentier B., Piérard G. E. Comparative immunohistochemical study of herpes simplex and varicella-zoster infections. Virchows Arch A Pathol Anat Histopathol. 1993;422(2):121–126. doi: 10.1007/BF01607163. [DOI] [PubMed] [Google Scholar]
- Ostrove J. M. Molecular biology of varicella zoster virus. Adv Virus Res. 1990;38:45–98. doi: 10.1016/s0065-3527(08)60859-3. [DOI] [PubMed] [Google Scholar]
- 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]
- Post L. E., Roizman B. A generalized technique for deletion of specific genes in large genomes: alpha gene 22 of herpes simplex virus 1 is not essential for growth. Cell. 1981 Jul;25(1):227–232. doi: 10.1016/0092-8674(81)90247-6. [DOI] [PubMed] [Google Scholar]
- Purves F. C., Ogle W. O., Roizman B. Processing of the herpes simplex virus regulatory protein alpha 22 mediated by the UL13 protein kinase determines the accumulation of a subset of alpha and gamma mRNAs and proteins in infected cells. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6701–6705. doi: 10.1073/pnas.90.14.6701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruyechan W. T., Weir A. C. Interaction with nucleic acids and stimulation of the viral DNA polymerase by the herpes simplex virus type 1 major DNA-binding protein. J Virol. 1984 Dec;52(3):727–733. doi: 10.1128/jvi.52.3.727-733.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sadzot-Delvaux C., Merville-Louis M. P., Delrée P., Marc P., Piette J., Moonen G., Rentier B. An in vivo model of varicella-zoster virus latent infection of dorsal root ganglia. J Neurosci Res. 1990 May;26(1):83–89. doi: 10.1002/jnr.490260110. [DOI] [PubMed] [Google Scholar]
- 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]
- Sears A. E., Halliburton I. W., Meignier B., Silver S., Roizman B. Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice. J Virol. 1985 Aug;55(2):338–346. doi: 10.1128/jvi.55.2.338-346.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sekulovich R. E., Leary K., Sandri-Goldin R. M. The herpes simplex virus type 1 alpha protein ICP27 can act as a trans-repressor or a trans-activator in combination with ICP4 and ICP0. J Virol. 1988 Dec;62(12):4510–4522. doi: 10.1128/jvi.62.12.4510-4522.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiraki K., Hyman R. W. The immediate early proteins of varicella-zoster virus. Virology. 1987 Feb;156(2):423–426. doi: 10.1016/0042-6822(87)90423-5. [DOI] [PubMed] [Google Scholar]
- Smith D. B., Davern K. M., Board P. G., Tiu W. U., Garcia E. G., Mitchell G. F. Mr 26,000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8703–8707. doi: 10.1073/pnas.83.22.8703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
- Vafai A., Murray R. S., Wellish M., Devlin M., Gilden D. H. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2362–2366. doi: 10.1073/pnas.85.7.2362. [DOI] [PMC free article] [PubMed] [Google Scholar]