1887

Abstract

Epstein–Barr virus (EBV) has been shown to infect T lymphocytes and to be associated with a chronic active infection (CAEBV), which has been recognized as a mainly non-neoplastic T-cell lymphoproliferative disorder (T-cell LPD). The systemic distribution of EBV genomes was studied, by real-time PCR, in multiple tissues from six patients with CAEBV, including three patients with T-cell LPD, one patient with B-cell LPD and two patients with undetermined cell-type LPD. There were extremely high loads of EBV genomes in all tissues from the patients. This reflects an abundance of circulating and infiltrating EBV-infected cells and a wide variety of clinical symptoms in the affected tissues. We chose one sample from each patient that was shown by real-time PCR to contain a high load of EBV genomes and examined the expression of EBV latent genes by RT–PCR. EBER1 and EBNA1 transcripts were detected in all samples. Only one sample also expressed EBNA2, LMP1 and LMP2A transcripts in addition to EBER1 and EBNA1 transcripts. Two of the remaining five samples expressed LMP1 and LMP2A transcripts. One sample expressed LMP2A but not LMP1 and EBNA2 transcripts. Another sample expressed EBNA2 but not LMP1 and LMP2A transcripts. The other sample did not express transcripts of any of the other EBNAs or LMPs. None of the samples expressed the viral immediate-early gene BZLF1. These results showed that EBV latent gene expression in CAEBV is heterogeneous and that restricted forms of EBV latency might play a pathogenic role in the development of CAEBV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-10-2385
2001-10-01
2019-10-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/10/0822385a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-10-2385&mimeType=html&fmt=ahah

References

  1. Baer, R., Bankier, A. T., Biggin, M. D., Deininger, P. L., Farrell, P. J., Gibson, T. J., Hatfall, G., Hudson, G. S., Satchwell, S. C., Séguin, C., Tuffnell, P. S. & Barrell, B. G. ( 1984; ). DNA sequence and expression of the B95-8 Epstein–Barr virus genome. Nature 310, 207-211.[CrossRef]
    [Google Scholar]
  2. Brooks, L., Yao, Q. Y., Rickinson, A. B. & Young, L. S. ( 1992; ). Epstein–Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. Journal of Virology 66, 2689-2697.
    [Google Scholar]
  3. Brooks, L. A., Lear, A. L., Young, L. S. & Rickinson, A. B. ( 1993; ). Transcripts from the Epstein–Barr virus BamHI A fragment are detectable in all three forms of virus latency. Journal of Virology 67, 3182-3190.
    [Google Scholar]
  4. Busson, P., McCoy, R., Sadler, R., Gilligan, K., Tursz, T. & Raab-Traub, N. ( 1992; ). Consistent transcription of the Epstein–Barr virus LMP2 gene in nasopharyngeal carcinoma. Journal of Virology 66, 3257-3262.
    [Google Scholar]
  5. Chen, F., Zou, J.-Z., di Renzo, L., Winberg, G., Hu, L.-F., Klein, E., Klein, G. & Ernberg, I. ( 1995; ). A subpopulation of normal B cells latently infected with Epstein–Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1. Journal of Virology 69, 3752-3758.
    [Google Scholar]
  6. Chen, H., Smith, P., Ambinder, R. F. & Hyward, S. D. ( 1999; ). Expression of Epstein–Barr virus BamHI-A rightward transcripts in latently infected B cells from peripheral blood. Blood 93, 3026-3032.
    [Google Scholar]
  7. Decker, L. L., Klaman, L. D. & Thorley-Lawson, D. A. ( 1996; ). Detection of the latent form of Epstein–Barr virus DNA in the peripheral blood of healthy individuals. Journal of Virology 70, 3286-3289.
    [Google Scholar]
  8. Faulkner, G. C., Krajewski, A. S. & Crawford, D. H. ( 2000; ). The ins and outs of EBV infection. Trends in Microbiology 8, 185-189.[CrossRef]
    [Google Scholar]
  9. Fujiwara, S. & Ono, Y. ( 1995; ). Isolation of Epstein–Barr virus-infected clones of the human T-cell line MT-2: use of recombinant viruses with a positive selection marker. Journal of Virology 69, 3900-3903.
    [Google Scholar]
  10. Griffin, B. E. ( 2000; ). Epstein–Barr virus (EBV) and human disease: facts, opinions and problems. Mutation Research 462, 395-405.[CrossRef]
    [Google Scholar]
  11. Harabuchi, Y., Yamanaka, N., Kataura, A., Imai, S., Kinoshita, T., Mizuno, F. & Osato, T. ( 1990; ). Epstein–Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet 335, 128-130.[CrossRef]
    [Google Scholar]
  12. Hsu, J. L. & Glaser, S. L. ( 2000; ). Epstein–Barr virus-associated malignancies: epidemiologic patterns and etiologic implications. Critical Reviews in Oncology/Hematology 34, 27-53.[CrossRef]
    [Google Scholar]
  13. Imai, S., Koizumi, S., Sugiura, M., Tokunaga, M., Uemura, Y., Yamamoto, N., Tanaka, S., Sato, E. & Osato, T. ( 1994; ). Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein–Barr virus latent infection protein. Proceedings of the National Academy of Sciences, USA 91, 9131-9135.[CrossRef]
    [Google Scholar]
  14. Imai, S., Sugiura, M., Oikawa, O., Koizumi, S., Hirao, M., Kimura, H., Hayashibara, H., Terai, N., Tsutsumi, H., Oda, T., Chiba, S. & Osato, T. ( 1996; ). Epstein–Barr virus (EBV)-carrying and -expressing T-cell lines established from severe chronic active EBV infection. Blood 87, 1446-1457.
    [Google Scholar]
  15. Jones, J. F., Shurin, S., Abramowsky, C., Tubbs, R. R., Sciotto, C. G., Wahl, R., Sands, J., Gottman, D., Katz, B. Z. & Sklar, J. ( 1988; ). T-cell lymphomas containing Epstein–Barr viral DNA in patients with chronic Epstein–Barr virus infections. New England Journal of Medicine 318, 733-741.[CrossRef]
    [Google Scholar]
  16. Kawaguchi, H., Miyashita, T., Herbst, H., Niedobitek, G., Asada, M., Tsuchida, M., Hanada, R., Kinoshita, A., Sakurai, M., Kobayashi, N. & Mizutani, S. ( 1993; ). Epstein–Barr virus-infected T lymphocytes in Epstein–Barr virus-associated hemophagocytic syndrome. Journal of Clinical Investigation 92, 1444-1450.[CrossRef]
    [Google Scholar]
  17. Kelleher, C. A., Paterson, R. K., Dreyfus, D. H., Streib, J. E., Xu, J. W., Takase, K., Jones, J. F. & Gelfand, E. W. ( 1995; ). Epstein–Barr virus replicative gene transcription during de novo infection of human thymocytes: simultaneous early expression of BZLF-1 and its repressor RAZ. Virology 208, 685-695.[CrossRef]
    [Google Scholar]
  18. Kikuta, H., Taguchi, Y., Tomizawa, K., Kojima, K., Kawamura, N., Ishizaka, A., Sakiyama, Y., Matsumoto, S., Imai, S., Kinoshita, T., Koizumi, S., Osato, T., Kobayashi, I., Hamada, I. & Hirai, K. ( 1988; ). Epstein–Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease. Nature 333, 455-457.[CrossRef]
    [Google Scholar]
  19. Kikuta, H., Nakanishi, M., Sakiyama, Y. & Matsumoto, S. ( 1989; ). Chronic active Epstein–Barr virus (EBV) infection is associated with clonotypic intracellular terminal regions of the EBV. Journal of Infectious Diseases 160, 546-547.[CrossRef]
    [Google Scholar]
  20. Kikuta, H., Sakiyama, Y., Matsumoto, S., Hamada, I., Yazaki, M., Iwaki, T. & Nakano, M. ( 1993; ). Detection of Epstein–Barr virus DNA in cardiac and aortic tissues from chronic, active Epstein–Barr virus infection associated with Kawasaki disease-like coronary artery aneurysms. Journal of Pediatrics 123, 90-92.[CrossRef]
    [Google Scholar]
  21. Kimura, H., Morita, M., Yabuta, Y., Kuzushima, K., Kato, K., Kojima, S., Matsuyama, T. & Morishima, T. ( 1999; ). Quantitative analysis of Epstein–Barr virus load by using a real-time PCR assay. Journal of Clinical Microbiology 37, 132-136.
    [Google Scholar]
  22. Klein, G. ( 1994; ). Epstein–Barr virus strategy in normal and neoplastic B cells. Cell 77, 791-793.[CrossRef]
    [Google Scholar]
  23. Koizumi, S., Zhang, X.-K., Imai, S., Sugiura, M., Usui, N. & Osato, T. ( 1992; ). Infection of the HTLV-1-harboring T-lymphoblastoid line MT-2 by Epstein–Barr virus. Virology 188, 859-863.[CrossRef]
    [Google Scholar]
  24. Maeda, A., Wakiguchi, H., Yokoyama, W., Hisakawa, H., Tomoda, T. & Kurashige, T. ( 1999; ). Persistently high Epstein-Barr virus (EBV) loads in peripheral blood lymphocytes from patients with chronic active EBV infection. Journal of Infectious Diseases 179, 1012-1015.[CrossRef]
    [Google Scholar]
  25. Miyashita, E. M., Yang, B., Lam, K. M. C., Crawford, D. H. & Thorley-Lawson, D. A. ( 1995; ). A novel form of Epstein–Barr virus latency in normal B cells in vivo. Cell 80, 593-601.[CrossRef]
    [Google Scholar]
  26. Miyashita, E. M., Yang, B., Babcock, G. J. & Thorley-Lawson, D. A. ( 1997; ). Identification of the site of Epstein–Barr virus persistence in vivo as a resting B cell. Journal of Virology 71, 4882-4891.
    [Google Scholar]
  27. Niedobitek, G., Agathanggelou, A., Rowe, M., Jones, D. B., Turyaguma, P., Oryema, J., Wright, D. H. & Young, L. S. ( 1995; ). Heterogeneous expression of Epstein–Barr virus latent proteins in endemic Burkitt’s lymphoma. Blood 86, 659-665.
    [Google Scholar]
  28. Ohga, S., Kimura, N., Takada, H., Nagano, M., Ohshima, K., Nomura, A., Muraoka, K., Take, H., Yamamori, S. & Hara, T. ( 1999; ). Restricted diversification of T-cells in chronic active Epstein–Barr virus infection: potential inclination to T-lymphoproliferative disease. American Journal of Hematology 61, 26-33.[CrossRef]
    [Google Scholar]
  29. Pallesen, G., Hamilton-Dutoit, S. J., Rowe, M. & Young, L. S. ( 1991; ). Expression of the Epstein–Barr virus latent gene products in tumor cells of Hodgkin’s disease. Lancet 337, 320-322.[CrossRef]
    [Google Scholar]
  30. Pallesen, G., Hamilton-Dutoit, S. J. & Zhou, X. ( 1993; ). The association of Epstein–Barr virus (EBV) with T cell lymphoproliferations and Hodgkin’s disease: two new developments in the EBV field. Advances in Cancer Research 62, 179-239.
    [Google Scholar]
  31. Paterson, R. L. K., Kelleher, C. A., Streib, J. E., Amankonah, T. D., Xu, J. W., Jones, J. F. & Gelfand, E. W. ( 1995; ). Activation of human thymocytes after infection by EBV. Journal of Immunology 154, 1440-1449.
    [Google Scholar]
  32. Rickinson, A. B. ( 1986; ). Chronic, symptomatic Epstein–Barr virus infections. Immunology Today 7, 13-14.[CrossRef]
    [Google Scholar]
  33. Rowe, M., Lear, A. L., Croom-Carter, D., Davies, A. H. & Rickinson, A. B. ( 1992; ). Three pathways of Epstein–Barr virus gene activation from EBNA1-positive latency in B lymphocytes. Journal of Virology 66, 122-131.
    [Google Scholar]
  34. Schaefer, B. C., Woisetschlaeger, M., Strominger, J. L. & Speck, S. H. ( 1991; ). Exclusive expression of Epstein–Barr virus nuclear antigen 1 in Burkitt lymphoma arises from a third promoter, distinct from the promoters used in latently infected lymphocytes. Proceedings of the National Academy of Sciences, USA 88, 6550-6554.[CrossRef]
    [Google Scholar]
  35. Schooley, R. T., Carey, R. W., Miller, G., Henle, W., Eastman, R., Mark, E. J., Kenyon, K., Wheeler, E. O. & Rubin, R. H. ( 1986; ). Chronic Epstein–Barr virus infection associated with fever and interstitial pneumonitis: clinical and serologic features and response to antiviral chemotherapy. Annals of Internal Medicine 104, 636-643.[CrossRef]
    [Google Scholar]
  36. Su, I.-J., Hsieh, H.-C., Lin, K.-H., Uen, W.-C., Kao, C.-L., Chen, C.-J., Cheng, A.-L., Kadin, M. E. & Chen, J.-Y. ( 1991; ). Aggressive peripheral T-cell lymphomas containing Epstein–Barr viral DNA: a clinicopathologic and molecular analysis. Blood 77, 799-808.
    [Google Scholar]
  37. Su, I.-J., Chen, R.-L., Lin, D.-T., Lin, K.-S. & Chen, C.-C. ( 1994; ). Epstein–Barr virus (EBV) infects T lymphocytes in childhood EBV-associated hemophagocytic syndrome in Taiwan. American Journal of Pathology 144, 1219-1225.
    [Google Scholar]
  38. Sugiyama, K., Ito, M., Ichimi, R., Higashikawa, M., Kawasaki, H., Komada, Y., Sakurai, M., Wakiguchi, H., Kikuta, H. & Fukayama, M. ( 1997; ). A case of Epstein–Barr virus infection with exophthalmos and ocular muscle swelling. Acta Paediatrica Japonica 39, 694-697.[CrossRef]
    [Google Scholar]
  39. Suzushima, H., Asou, N., Fujimoto, T., Nishimura, S., Okubo, H., Yamasaki, H., Osato, M., Matsuoka, M., Tsukamoto, A., Takai, K., Kawano, F. & Takatsuki, K. ( 1995; ). Lack of the expression of EBNA-2 and LMP-1 in T-cell neoplasms possessing Epstein–Barr virus. Blood 85, 480-486.
    [Google Scholar]
  40. Takada, K., Shimizu, N., Sakuma, S. & Ono, Y. ( 1986; ). Trans activation of the latent Epstein–Barr virus (EBV) genome after transfection of the EBV DNA fragment. Journal of Virology 57, 1016-1022.
    [Google Scholar]
  41. Thorley-Lawson, D. A. & Babcock, G. J. ( 1999; ). A model for persistent infection with Epstein–Barr virus: the stealth virus of human B cells. Life Sciences 65, 1433-1453.[CrossRef]
    [Google Scholar]
  42. Thorley-Lawson, D. A., Miyashita, E. M. & Khan, G. ( 1996; ). Epstein–Barr virus and B cells: that’s all it takes. Trends in Microbiology 4, 204-208.[CrossRef]
    [Google Scholar]
  43. Tierney, R. J., Steven, N., Young, L. S. & Rickinson, A. B. ( 1994; ). Epstein–Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. Journal of Virology 68, 7374-7385.
    [Google Scholar]
  44. Zetterberg, H., Stenglein, M., Jansson, A., Ricksten, A. & Rymo, L. ( 1999; ). Relative levels of EBNA1 gene transcripts from the C/W, F and Q promoters in Epstein–Barr virus-transformed lymphoid cells in latent and lytic stages of infection. Journal of General Virology 80, 457-465.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-10-2385
Loading
/content/journal/jgv/10.1099/0022-1317-82-10-2385
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error