Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1995 Nov;69(11):7309–7314. doi: 10.1128/jvi.69.11.7309-7314.1995

The lytic cycle of Epstein-Barr virus in the nonproducer Raji line can be rescued by the expression of a 135-kilodalton protein encoded by the BALF2 open reading frame.

G Decaussin 1, V Leclerc 1, T Ooka 1
PMCID: PMC189660  PMID: 7474160

Abstract

In Epstein-Barr virus (EBV)-carrying nonproducer Raji cells, the induction of the viral replicative cycle by chemical treatment is limited to only the early stage and viral DNA synthesis is totally inhibited. We previously showed the absence of two messenger RNAs that are encoded by the BamHI-A fragment of the EBV genome and that correspond to open reading frames BALF2 and BARF1 in chemically induced Raji cells. Since the BALF2 gene encodes a 135-kDa DNA-binding protein which was immunoprecipitated by antibody against ICP8 protein, a key protein in herpes simplex virus replication, we asked whether the lack of productive cycle in Raji cells is due to the absence of expression of the BALF2 gene. We transfected the Raji cell line with the BALF2 gene. After chemical induction, the BALF2-transfected cells expressed not only early antigens but also late antigens. In these cultures, the viral particles were detected by electron microscopy. The expression of late antigens was completely inhibited by arabinofuranosylthymine, which is a specific inhibitor of viral DNA replication. The BALF2 gene might play an essential role in the induction of the EBV-lytic cycle.

Full Text

The Full Text of this article is available as a PDF (717.9 KB).

Selected References

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

  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  2. Biggin M., Bodescot M., Perricaudet M., Farrell P. Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells. J Virol. 1987 Oct;61(10):3120–3132. doi: 10.1128/jvi.61.10.3120-3132.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boehmer P. E., Lehman I. R. Physical interaction between the herpes simplex virus 1 origin-binding protein and single-stranded DNA-binding protein ICP8. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8444–8448. doi: 10.1073/pnas.90.18.8444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Eckhardt S., Badellino F., Murphy G. P. UICC meeting on breast-cancer screening in pre-menopausal women in developed countries. Geneva, 29 September-1 October 1993. Int J Cancer. 1994 Jan 2;56(1):1–5. doi: 10.1002/ijc.2910560102. [DOI] [PubMed] [Google Scholar]
  5. Gao M., Bouchey J., Curtin K., Knipe D. M. Genetic identification of a portion of the herpes simplex virus ICP8 protein required for DNA-binding. Virology. 1988 Apr;163(2):319–329. doi: 10.1016/0042-6822(88)90272-3. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Gong M., Ooka T., Matsuo T., Kieff E. Epstein-Barr virus glycoprotein homologous to herpes simplex virus gB. J Virol. 1987 Feb;61(2):499–508. doi: 10.1128/jvi.61.2.499-508.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hampar B., Derge J. G., Nonoyama M., Chang S. Y., Tagamets A., Showalter S. D. Programming of events in Epstein-Barr virus-activated cells induced by 5-iododeoxyuridine. Virology. 1974 Nov;62(1):71–89. doi: 10.1016/0042-6822(74)90304-3. [DOI] [PubMed] [Google Scholar]
  9. Hatfull G., Bankier A. T., Barrell B. G., Farrell P. J. Sequence analysis of Raji Epstein-Barr virus DNA. Virology. 1988 Jun;164(2):334–340. doi: 10.1016/0042-6822(88)90546-6. [DOI] [PubMed] [Google Scholar]
  10. Henle G., Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. doi: 10.1128/jb.91.3.1248-1256.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kallin B., Klein G. Epstein-Barr virus carried by Raji cells: a mutant in early functions? Intervirology. 1983;19(1):47–51. doi: 10.1159/000149336. [DOI] [PubMed] [Google Scholar]
  12. Lin J. C., De B. K., Mar E. C. Functional characterization of partially purified Epstein-Barr virus DNA polymerase expressed in the baculovirus system. Virus Genes. 1994 Jul;8(3):231–241. doi: 10.1007/BF01704517. [DOI] [PubMed] [Google Scholar]
  13. O'Donnell M. E., Elias P., Funnell B. E., Lehman I. R. Interaction between the DNA polymerase and single-stranded DNA-binding protein (infected cell protein 8) of herpes simplex virus 1. J Biol Chem. 1987 Mar 25;262(9):4260–4266. [PubMed] [Google Scholar]
  14. Ooka T., Calender A. Effects of arabinofuranosylthymine on Epstein-Barr virus replication. Virology. 1980 Jul 15;104(1):219–223. doi: 10.1016/0042-6822(80)90379-7. [DOI] [PubMed] [Google Scholar]
  15. Ooka T., Calender A., de Turenne M., Daillie J. Effect of arabinofuranosylthymine on the replication of Epstein-Barr virus and relationship with a new induced thymidine kinase activity. J Virol. 1983 Apr;46(1):187–195. doi: 10.1128/jvi.46.1.187-195.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ooka T., De Turenne M., De The G., Daillie J. Epstein-Barr virus-specific DNase activity in nonproducer Raji cells after treatment with 12-o-tetradecanoylphorbol-13-acetate and sodium butyrate. J Virol. 1984 Feb;49(2):626–628. doi: 10.1128/jvi.49.2.626-628.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ooka T., Lenoir G. M., Decaussin G., Bornkamm G. W., Daillie J. Epstein-Barr virus-specific DNA polymerase in virus-nonproducer Raji cells. J Virol. 1986 May;58(2):671–675. doi: 10.1128/jvi.58.2.671-675.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ooka T., Lenoir G., Daillie J. Characterization of an Epstein-Barr virus-induced DNA polymerase. J Virol. 1979 Jan;29(1):1–10. doi: 10.1128/jvi.29.1.1-10.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Polack A., Delius H., Zimber U., Bornkamm G. W. Two deletions in the Epstein-Barr virus genome of the Burkitt lymphoma nonproducer line Raji. Virology. 1984 Feb;133(1):146–157. doi: 10.1016/0042-6822(84)90433-1. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Quinn J. P., McGeoch D. J. DNA sequence of the region in the genome of herpes simplex virus type 1 containing the genes for DNA polymerase and the major DNA binding protein. Nucleic Acids Res. 1985 Nov 25;13(22):8143–8163. doi: 10.1093/nar/13.22.8143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ruyechan W. T. The major herpes simplex virus DNA-binding protein holds single-stranded DNA in an extended configuration. J Virol. 1983 May;46(2):661–666. doi: 10.1128/jvi.46.2.661-666.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tanner J., Weis J., Fearon D., Whang Y., Kieff E. Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell. 1987 Jul 17;50(2):203–213. doi: 10.1016/0092-8674(87)90216-9. [DOI] [PubMed] [Google Scholar]
  24. Tomkinson B., Robertson E., Kieff E. Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. J Virol. 1993 Apr;67(4):2014–2025. doi: 10.1128/jvi.67.4.2014-2025.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Toneguzzo F., Hayday A. C., Keating A. Electric field-mediated DNA transfer: transient and stable gene expression in human and mouse lymphoid cells. Mol Cell Biol. 1986 Feb;6(2):703–706. doi: 10.1128/mcb.6.2.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wei M. X., Moulin J. C., Decaussin G., Berger F., Ooka T. Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human Louckes B-lymphocyte cell line. Cancer Res. 1994 Apr 1;54(7):1843–1848. [PubMed] [Google Scholar]
  27. Wei M. X., Ooka T. A transforming function of the BARF1 gene encoded by Epstein-Barr virus. EMBO J. 1989 Oct;8(10):2897–2903. doi: 10.1002/j.1460-2075.1989.tb08438.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weller S. K., Lee K. J., Sabourin D. J., Schaffer P. A. Genetic analysis of temperature-sensitive mutants which define the gene for the major herpes simplex virus type 1 DNA-binding protein. J Virol. 1983 Jan;45(1):354–366. doi: 10.1128/jvi.45.1.354-366.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [DOI] [PubMed] [Google Scholar]
  30. Zhang C. X., Decaussin G., Daillie J., Ooka T. Altered expression of two Epstein-Barr virus early genes localized in BamHI-A in nonproducer Raji cells. J Virol. 1988 Jun;62(6):1862–1869. doi: 10.1128/jvi.62.6.1862-1869.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zhang C. X., Decaussin G., Finerty S., Morgan A., Ooka T. Transcriptional expression of the viral genome in the Epstein-Barr virus-induced tamarin lymphoma and the corresponding lymphoblastoid tumour lines. Virus Res. 1992 Nov;26(2):153–166. doi: 10.1016/0168-1702(92)90154-2. [DOI] [PubMed] [Google Scholar]
  32. de Bruyn Kops A., Knipe D. M. Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein. Cell. 1988 Dec 2;55(5):857–868. doi: 10.1016/0092-8674(88)90141-9. [DOI] [PubMed] [Google Scholar]
  33. de Turenne-Tessier M., Ooka T., de The G., Daillie J. Characterization of an Epstein-Barr virus-induced thymidine kinase. J Virol. 1986 Mar;57(3):1105–1112. doi: 10.1128/jvi.57.3.1105-1112.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. van Grunsven W. M., van Heerde E. C., de Haard H. J., Spaan W. J., Middeldorp J. M. Gene mapping and expression of two immunodominant Epstein-Barr virus capsid proteins. J Virol. 1993 Jul;67(7):3908–3916. doi: 10.1128/jvi.67.7.3908-3916.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. zur Hausen H., O'Neill F. J., Freese U. K., Hecker E. Persisting oncogenic herpesvirus induced by the tumour promotor TPA. Nature. 1978 Mar 23;272(5651):373–375. doi: 10.1038/272373a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES