Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1995 Dec;69(12):8155–8158. doi: 10.1128/jvi.69.12.8155-8158.1995

Epstein-Barr virus induction of recombinase-activating genes RAG1 and RAG2.

S K Srinivas 1, J W Sixbey 1
PMCID: PMC189773  PMID: 7494341

Abstract

In experimental B-cell infections, Epstein-Barr virus induced sustained expression of V(D)J recombinase-activating genes RAG1 and RAG2, whose aberrant activity has been implicated in chromosomal translocations in B-cell neoplasms. In cell lines in which RAG1 and RAG2 were detected, virus integrated into cellular DNA rather than assumed the configuration of extrachromosomal episomes. Expression of the Epstein-Barr virus nuclear antigen 1 in transient transfection assays was sufficient to induce both recombinase-activating genes.

Full Text

The Full Text of this article is available as a PDF (243.0 KB).

Selected References

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

  1. Adams A., Lindahl T. Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1477–1481. doi: 10.1073/pnas.72.4.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aster J. C., Kobayashi Y., Shiota M., Mori S., Sklar J. Detection of the t(14;18) at similar frequencies in hyperplastic lymphoid tissues from American and Japanese patients. Am J Pathol. 1992 Aug;141(2):291–299. [PMC free article] [PubMed] [Google Scholar]
  3. Benson J. D., Huang E. S. Human cytomegalovirus induces expression of cellular topoisomerase II. J Virol. 1990 Jan;64(1):9–15. doi: 10.1128/jvi.64.1.9-15.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berger S. L., Birkenmeier C. S. Inhibition of intractable nucleases with ribonucleoside--vanadyl complexes: isolation of messenger ribonucleic acid from resting lymphocytes. Biochemistry. 1979 Nov 13;18(23):5143–5149. doi: 10.1021/bi00590a018. [DOI] [PubMed] [Google Scholar]
  5. Bories J. C., Cayuela J. M., Loiseau P., Sigaux F. Expression of human recombination activating genes (RAG1 and RAG2) in neoplastic lymphoid cells: correlation with cell differentiation and antigen receptor expression. Blood. 1991 Oct 15;78(8):2053–2061. [PubMed] [Google Scholar]
  6. Calender A., Billaud M., Aubry J. P., Banchereau J., Vuillaume M., Lenoir G. M. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060–8064. doi: 10.1073/pnas.84.22.8060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carlson L. M., Oettinger M. A., Schatz D. G., Masteller E. L., Hurley E. A., McCormack W. T., Baltimore D., Thompson C. B. Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene conversion. Cell. 1991 Jan 11;64(1):201–208. doi: 10.1016/0092-8674(91)90221-j. [DOI] [PubMed] [Google Scholar]
  8. Cho M. S., Gissmann L., Hayward S. D. Epstein-Barr virus (P3HR-1) defective DNA codes for components of both the early antigen and viral capsid antigen complexes. Virology. 1984 Aug;137(1):9–19. doi: 10.1016/0042-6822(84)90003-5. [DOI] [PubMed] [Google Scholar]
  9. Ebert S. N., Subramanian D., Shtrom S. S., Chung I. K., Parris D. S., Muller M. T. Association between the p170 form of human topoisomerase II and progeny viral DNA in cells infected with herpes simplex virus type 1. J Virol. 1994 Feb;68(2):1010–1020. doi: 10.1128/jvi.68.2.1010-1020.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  11. Gardella T., Medveczky P., Sairenji T., Mulder C. Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis. J Virol. 1984 Apr;50(1):248–254. doi: 10.1128/jvi.50.1.248-254.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haluska F. G., Finver S., Tsujimoto Y., Croce C. M. The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature. 1986 Nov 13;324(6093):158–161. doi: 10.1038/324158a0. [DOI] [PubMed] [Google Scholar]
  13. Hurley E. A., Agger S., McNeil J. A., Lawrence J. B., Calendar A., Lenoir G., Thorley-Lawson D. A. When Epstein-Barr virus persistently infects B-cell lines, it frequently integrates. J Virol. 1991 Mar;65(3):1245–1254. doi: 10.1128/jvi.65.3.1245-1254.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ichihara Y., Hirai M., Kurosawa Y. Sequence and chromosome assignment to 11p13-p12 of human RAG genes. Immunol Lett. 1992 Aug;33(3):277–284. doi: 10.1016/0165-2478(92)90073-w. [DOI] [PubMed] [Google Scholar]
  15. Jenson H. B., Miller G. Polymorphisms of the region of the Epstein-Barr virus genome which disrupts latency. Virology. 1988 Aug;165(2):549–564. doi: 10.1016/0042-6822(88)90599-5. [DOI] [PubMed] [Google Scholar]
  16. Kawanishi M. Topoisomerase I and II activities are required for Epstein-Barr virus replication. J Gen Virol. 1993 Oct;74(Pt 10):2263–2268. doi: 10.1099/0022-1317-74-10-2263. [DOI] [PubMed] [Google Scholar]
  17. King W., Dambaugh T., Heller M., Dowling J., Kieff E. Epstein-Barr virus DNA XII. A variable region of the Epstein-Barr virus genome is included in the P3HR-1 deletion. J Virol. 1982 Sep;43(3):979–986. doi: 10.1128/jvi.43.3.979-986.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuhn-Hallek I., Sage D. R., Stein L., Groelle H., Fingeroth J. D. Expression of recombination activating genes (RAG-1 and RAG-2) in Epstein-Barr virus-bearing B cells. Blood. 1995 Mar 1;85(5):1289–1299. [PubMed] [Google Scholar]
  19. Lee E. S., Locker J., Nalesnik M., Reyes J., Jaffe R., Alashari M., Nour B., Tzakis A., Dickman P. S. The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation. N Engl J Med. 1995 Jan 5;332(1):19–25. doi: 10.1056/NEJM199501053320104. [DOI] [PubMed] [Google Scholar]
  20. Limpens J., de Jong D., van Krieken J. H., Price C. G., Young B. D., van Ommen G. J., Kluin P. M. Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Oncogene. 1991 Dec;6(12):2271–2276. [PubMed] [Google Scholar]
  21. Lin W. C., Desiderio S. Cell cycle regulation of V(D)J recombination-activating protein RAG-2. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2733–2737. doi: 10.1073/pnas.91.7.2733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lipkowitz S., Garry V. F., Kirsch I. R. Interlocus V-J recombination measures genomic instability in agriculture workers at risk for lymphoid malignancies. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5301–5305. doi: 10.1073/pnas.89.12.5301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Liu Y., Hernandez A. M., Shibata D., Cortopassi G. A. BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8910–8914. doi: 10.1073/pnas.91.19.8910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ma A., Fisher P., Dildrop R., Oltz E., Rathbun G., Achacoso P., Stall A., Alt F. W. Surface IgM mediated regulation of RAG gene expression in E mu-N-myc B cell lines. EMBO J. 1992 Jul;11(7):2727–2734. doi: 10.1002/j.1460-2075.1992.tb05338.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Marshall D., Sample C. Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator. J Virol. 1995 Jun;69(6):3624–3630. doi: 10.1128/jvi.69.6.3624-3630.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murray R. J., Young L. S., Calender A., Gregory C. D., Rowe M., Lenoir G. M., Rickinson A. B. Different patterns of Epstein-Barr virus gene expression and of cytotoxic T-cell recognition in B-cell lines infected with transforming (B95.8) or nontransforming (P3HR1) virus strains. J Virol. 1988 Mar;62(3):894–901. doi: 10.1128/jvi.62.3.894-901.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nonoyama M., Pagano J. S. Separation of Epstein-Barr virus DNA from large chromosomal DNA in non-virus-producing cells. Nat New Biol. 1972 Aug 9;238(84):169–171. doi: 10.1038/newbio238169a0. [DOI] [PubMed] [Google Scholar]
  28. Oettinger M. A., Schatz D. G., Gorka C., Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990 Jun 22;248(4962):1517–1523. doi: 10.1126/science.2360047. [DOI] [PubMed] [Google Scholar]
  29. Patton D. F., Shirley P., Raab-Traub N., Resnick L., Sixbey J. W. Defective viral DNA in Epstein-Barr virus-associated oral hairy leukoplakia. J Virol. 1990 Jan;64(1):397–400. doi: 10.1128/jvi.64.1.397-400.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Raab-Traub N., Flynn K. The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell. 1986 Dec 26;47(6):883–889. doi: 10.1016/0092-8674(86)90803-2. [DOI] [PubMed] [Google Scholar]
  31. Rabson M., Gradoville L., Heston L., Miller G. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye. J Virol. 1982 Dec;44(3):834–844. doi: 10.1128/jvi.44.3.834-844.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rawlins D. R., Milman G., Hayward S. D., Hayward G. S. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985 Oct;42(3):859–868. doi: 10.1016/0092-8674(85)90282-x. [DOI] [PubMed] [Google Scholar]
  33. Reisman D., Yates J., Sugden B. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol. 1985 Aug;5(8):1822–1832. doi: 10.1128/mcb.5.8.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rowe D. T., Rowe M., Evan G. I., Wallace L. E., Farrell P. J., Rickinson A. B. Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells. EMBO J. 1986 Oct;5(10):2599–2607. doi: 10.1002/j.1460-2075.1986.tb04540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schatz D. G., Oettinger M. A., Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989 Dec 22;59(6):1035–1048. doi: 10.1016/0092-8674(89)90760-5. [DOI] [PubMed] [Google Scholar]
  36. Sixbey J. W., Shirley P., Sloas M., Raab-Traub N., Israele V. A transformation-incompetent, nuclear antigen 2-deleted Epstein-Barr virus associated with replicative infection. J Infect Dis. 1991 May;163(5):1008–1015. doi: 10.1093/infdis/163.5.1008. [DOI] [PubMed] [Google Scholar]
  37. Sun R., Spain T. A., Lin S. F., Miller G. Autoantigenic proteins that bind recombinogenic sequences in Epstein-Barr virus and cellular DNA. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8646–8650. doi: 10.1073/pnas.91.18.8646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Walling D. M., Clark N. M., Markovitz D. M., Frank T. S., Braun D. K., Eisenberg E., Krutchkoff D. J., Felix D. H., Raab-Traub N. Epstein-Barr virus coinfection and recombination in non-human immunodeficiency virus-associated oral hairy leukoplakia. J Infect Dis. 1995 May;171(5):1122–1130. doi: 10.1093/infdis/171.5.1122. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]
  42. Zimmermann J., Hammerschmidt W. Structure and role of the terminal repeats of Epstein-Barr virus in processing and packaging of virion DNA. J Virol. 1995 May;69(5):3147–3155. doi: 10.1128/jvi.69.5.3147-3155.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES