Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1995 Aug 1;14(15):3706–3711. doi: 10.1002/j.1460-2075.1995.tb00040.x

Persistent Epstein-Barr virus infection in a human T-cell line: unique program of latent virus expression.

H Yoshiyama 1, N Shimizu 1, K Takada 1
PMCID: PMC394445  PMID: 7641689

Abstract

The growth transforming potential of Epstein-Barr virus (EBV) for Burkitt's lymphoma and nasopharyngeal carcinoma is now extended to other neoplasia, such as Hodgkin's disease, peripheral T-cell tumor and gastric cancer. We have generated an EBV recombinant with a selectable marker at the viral thymidine kinase locus. Recombinant EBV was successfully infected into a human T-cell line, MT-2. Following incubation in the selective medium, drug resistant MT-2 cell clones were isolated and proved to be infected with recombinant EBV. EBV-infected MT-2 cell clones expressed EBNA 1 and LMP 1 and very little of EBNA 2, showing the BamHI F promoter-driven latency II form of infection, which is seen in non-B-cell tumors. This is the first report of in vitro generation of latency II type EBV infection. The present system of persistent EBV infection in T cells should be a good model for investigating the pathogenic role of EBV in non-B-cell tumors.

Full text

PDF
3706

Images in this article

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. Brooks L. A., Lear A. L., Young L. S., Rickinson A. B. Transcripts from the Epstein-Barr virus BamHI A fragment are detectable in all three forms of virus latency. J Virol. 1993 Jun;67(6):3182–3190. doi: 10.1128/jvi.67.6.3182-3190.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Deacon E. M., Pallesen G., Niedobitek G., Crocker J., Brooks L., Rickinson A. B., Young L. S. Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med. 1993 Feb 1;177(2):339–349. doi: 10.1084/jem.177.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Harabuchi Y., Yamanaka N., Kataura A., Imai S., Kinoshita T., Mizuno F., Osato T. Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet. 1990 Jan 20;335(8682):128–130. doi: 10.1016/0140-6736(90)90002-m. [DOI] [PubMed] [Google Scholar]
  7. Hurley E. A., Thorley-Lawson D. A. B cell activation and the establishment of Epstein-Barr virus latency. J Exp Med. 1988 Dec 1;168(6):2059–2075. doi: 10.1084/jem.168.6.2059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Koizumi S., Zhang X. K., Imai S., Sugiura M., Usui N., Osato T. Infection of the HTLV-I-harbouring T-lymphoblastoid line MT-2 by Epstein-Barr virus. Virology. 1992 Jun;188(2):859–863. doi: 10.1016/0042-6822(92)90542-w. [DOI] [PubMed] [Google Scholar]
  9. Korman A. J., Frantz J. D., Strominger J. L., Mulligan R. C. Expression of human class II major histocompatibility complex antigens using retrovirus vectors. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2150–2154. doi: 10.1073/pnas.84.8.2150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liebowitz D., Mannick J., Takada K., Kieff E. Phenotypes of Epstein-Barr virus LMP1 deletion mutants indicate transmembrane and amino-terminal cytoplasmic domains necessary for effects in B-lymphoma cells. J Virol. 1992 Jul;66(7):4612–4616. doi: 10.1128/jvi.66.7.4612-4616.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Minarovits J., Hu L. F., Imai S., Harabuchi Y., Kataura A., Minarovits-Kormuta S., Osato T., Klein G. Clonality, expression and methylation patterns of the Epstein-Barr virus genomes in lethal midline granulomas classified as peripheral angiocentric T cell lymphomas. J Gen Virol. 1994 Jan;75(Pt 1):77–84. doi: 10.1099/0022-1317-75-1-77. [DOI] [PubMed] [Google Scholar]
  12. Miyoshi I., Kubonishi I., Yoshimoto S., Akagi T., Ohtsuki Y., Shiraishi Y., Nagata K., Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
  13. Ohtsu T., Tsugane S., Tobinai K., Shimoyama M., Nanri S., Watanabe S. Prevalence of antibodies to human T-cell leukemia/lymphoma virus type I and human immunodeficiency virus in Japanese immigrant colonies in Bolivia and Bolivian natives. Jpn J Cancer Res. 1987 Dec;78(12):1347–1353. [PubMed] [Google Scholar]
  14. Patel R. A., Hutt-Fletcher L. M., Crews F. T. Epstein-Barr virus infectivity of Raji and Molt 4 cells: differences in cellular membrane lipids and apparent microviscosity. Virology. 1993 Jul;195(1):121–131. doi: 10.1006/viro.1993.1352. [DOI] [PubMed] [Google Scholar]
  15. Qu L., Rowe D. T. Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes. J Virol. 1992 Jun;66(6):3715–3724. doi: 10.1128/jvi.66.6.3715-3724.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rowe M., Evans H. S., Young L. S., Hennessy K., Kieff E., Rickinson A. B. Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells. J Gen Virol. 1987 Jun;68(Pt 6):1575–1586. doi: 10.1099/0022-1317-68-6-1575. [DOI] [PubMed] [Google Scholar]
  17. Rowe M., Lear A. L., Croom-Carter D., Davies A. H., Rickinson A. B. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol. 1992 Jan;66(1):122–131. doi: 10.1128/jvi.66.1.122-131.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shibata D., Tokunaga M., Uemura Y., Sato E., Tanaka S., Weiss L. M. Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like carcinoma. Am J Pathol. 1991 Sep;139(3):469–474. [PMC free article] [PubMed] [Google Scholar]
  19. Shimizu N., Tanabe-Tochikura A., Kuroiwa Y., Takada K. Isolation of Epstein-Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt's lymphoma (BL) line Akata: malignant phenotypes of BL cells are dependent on EBV. J Virol. 1994 Sep;68(9):6069–6073. doi: 10.1128/jvi.68.9.6069-6073.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sinha S. K., Todd S. C., Hedrick J. A., Speiser C. L., Lambris J. D., Tsoukas C. D. Characterization of the EBV/C3d receptor on the human Jurkat T cell line: evidence for a novel transcript. J Immunol. 1993 Jun 15;150(12):5311–5320. [PubMed] [Google Scholar]
  21. Takada K. Cross-linking of cell surface immunoglobulins induces Epstein-Barr virus in Burkitt lymphoma lines. Int J Cancer. 1984 Jan 15;33(1):27–32. doi: 10.1002/ijc.2910330106. [DOI] [PubMed] [Google Scholar]
  22. Takada K., Ono Y. Synchronous and sequential activation of latently infected Epstein-Barr virus genomes. J Virol. 1989 Jan;63(1):445–449. doi: 10.1128/jvi.63.1.445-449.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsoukas C. D., Lambris J. D. Expression of EBV/C3d receptors on T cells: biological significance. Immunol Today. 1993 Feb;14(2):56–59. doi: 10.1016/0167-5699(93)90059-T. [DOI] [PubMed] [Google Scholar]
  24. Wang D., Liebowitz D., Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell. 1985 Dec;43(3 Pt 2):831–840. doi: 10.1016/0092-8674(85)90256-9. [DOI] [PubMed] [Google Scholar]
  25. Watry D., Hedrick J. A., Siervo S., Rhodes G., Lamberti J. J., Lambris J. D., Tsoukas C. D. Infection of human thymocytes by Epstein-Barr virus. J Exp Med. 1991 Apr 1;173(4):971–980. doi: 10.1084/jem.173.4.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weiss L. M., Movahed L. A., Warnke R. A., Sklar J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl J Med. 1989 Feb 23;320(8):502–506. doi: 10.1056/NEJM198902233200806. [DOI] [PubMed] [Google Scholar]
  27. 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]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES