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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Nov;143(5):1263–1268.

Epstein-Barr virus in adult T-cell leukemia/lymphoma.

M Tokunaga 1, S Imai 1, Y Uemura 1, T Tokudome 1, T Osato 1, E Sato 1
PMCID: PMC1887181  PMID: 8238243

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a well-known human T-cell lymphotropic virus type-1-related disease. We studied Epstein-Barr virus (EBV) in the tumor cells of ATLL, to investigate the etiological significance of double infection with these viruses. We used polymerase chain reaction and EBV-encoded small RNA-1 in situ hybridization to investigate the presence of EBV and immunohistochemistry to detect EBV-related oncoproteins, such as EBV-determined nuclear antigen-2 and latent membrane protein. Polymerase chain reaction performed on DNA of frozen specimens from 96 cases of ATLL revealed that the tumor tissue from 21 cases contained EBV DNA. EBV-encoded small RNA-1 in situ hybridization performed on the paraffin sections of the polymerase chain reaction-positive cases indicated EBV in the nuclei of ATLL tumor cells in 16 cases, nine of which were in the pleomorphic nuclei. Latent membrane protein was also detected in the cytoplasm of ATLL tumor cells in 15 cases, and EBV nuclear antigen-2 was observed in the nuclei of ATLL tumor cells in 11 cases. We conclude that EBV was present within tumor cells in about 17% of cases with ATLL and expressed EBV oncoprotein in the tumor cells. It is hypothesized that EBV and human T-cell lymphotropic virus-1 may infect the same T cells in early life and may play a role in the oncogenesis of ATLL.

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  1. Blattner W. A., Kalyanaraman V. S., Robert-Guroff M., Lister T. A., Galton D. A., Sarin P. S., Crawford M. H., Catovsky D., Greaves M., Gallo R. C. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma. Int J Cancer. 1982 Sep 15;30(3):257–264. doi: 10.1002/ijc.2910300302. [DOI] [PubMed] [Google Scholar]
  2. Chang K. L., Chen Y. Y., Shibata D., Weiss L. M. Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues. Diagn Mol Pathol. 1992 Dec;1(4):246–255. [PubMed] [Google Scholar]
  3. EPSTEIN M. A., ACHONG B. G., BARR Y. M. VIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA. Lancet. 1964 Mar 28;1(7335):702–703. doi: 10.1016/s0140-6736(64)91524-7. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ho F. C., Srivastava G., Loke S. L., Fu K. H., Leung B. P., Liang R., Choy D. Presence of Epstein-Barr virus DNA in nasal lymphomas of B and 'T' cell type. Hematol Oncol. 1990 Sep-Oct;8(5):271–281. doi: 10.1002/hon.2900080505. [DOI] [PubMed] [Google Scholar]
  7. Jones J. F., Shurin S., Abramowsky C., Tubbs R. R., Sciotto C. G., Wahl R., Sands J., Gottman D., Katz B. Z., Sklar J. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med. 1988 Mar 24;318(12):733–741. doi: 10.1056/NEJM198803243181203. [DOI] [PubMed] [Google Scholar]
  8. Kai C., Okada N., Okada H. Expression of CR2 (C3d receptor) on the cell membranes of adult T cell leukemia. Jpn J Cancer Res. 1988 Jul;79(7):805–808. doi: 10.1111/j.1349-7006.1988.tb00039.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kikuta H., Taguchi Y., Tomizawa K., Kojima K., Kawamura N., Ishizaka A., Sakiyama Y., Matsumoto S., Imai S., Kinoshita T. Epstein-Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease. Nature. 1988 Jun 2;333(6172):455–457. doi: 10.1038/333455a0. [DOI] [PubMed] [Google Scholar]
  10. MacMahon E. M., Glass J. D., Hayward S. D., Mann R. B., Becker P. S., Charache P., McArthur J. C., Ambinder R. F. Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet. 1991 Oct 19;338(8773):969–973. doi: 10.1016/0140-6736(91)91837-k. [DOI] [PubMed] [Google Scholar]
  11. Mochizuki S., Kawamura K., Maruyama K. Virus production and surface marker expression in human lymphocytes immortalized following dual infection with human T-cell leukemia virus and Epstein-Barr virus. Int J Cancer. 1986 Apr 15;37(4):551–556. doi: 10.1002/ijc.2910370413. [DOI] [PubMed] [Google Scholar]
  12. Ohshima K., Kikuchi M., Eguchi F., Masuda Y., Sumiyoshi Y., Mohtai H., Takeshita M., Kimura N. Analysis of Epstein-Barr viral genomes in lymphoid malignancy using Southern blotting, polymerase chain reaction and in situ hybridization. Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;59(6):383–390. doi: 10.1007/BF02899428. [DOI] [PubMed] [Google Scholar]
  13. Pallesen G., Hamilton-Dutoit S. J., Rowe M., Young L. S. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991 Feb 9;337(8737):320–322. doi: 10.1016/0140-6736(91)90943-j. [DOI] [PubMed] [Google Scholar]
  14. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rowe M., Rowe D. T., Gregory C. D., Young L. S., Farrell P. J., Rupani H., Rickinson A. B. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells. EMBO J. 1987 Sep;6(9):2743–2751. doi: 10.1002/j.1460-2075.1987.tb02568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shibata D., Weiss L. M., Nathwani B. N., Brynes R. K., Levine A. M. Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin's lymphoma. Blood. 1991 Apr 1;77(7):1527–1533. [PubMed] [Google Scholar]
  17. Staal S. P., Ambinder R., Beschorner W. E., Hayward G. S., Mann R. A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease. Am J Clin Pathol. 1989 Jan;91(1):1–5. doi: 10.1093/ajcp/91.1.1. [DOI] [PubMed] [Google Scholar]
  18. 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. Aggressive peripheral T-cell lymphomas containing Epstein-Barr viral DNA: a clinicopathologic and molecular analysis. Blood. 1991 Feb 15;77(4):799–808. [PubMed] [Google Scholar]
  19. Suchi T., Tajima K., Nanba K., Wakasa H., Mikata A., Kikuchi M., Mori S., Watanabe S., Mohri N., Shamoto M. Some problems on the histopathological diagnosis of non-Hodgkin's malignant lymphoma -- a proposal of a new type. Acta Pathol Jpn. 1979 Sep;29(5):755–776. doi: 10.1111/j.1440-1827.1979.tb00942.x. [DOI] [PubMed] [Google Scholar]
  20. Takada K., Osato T. Analysis of the transformation of human lymphocytes by Epstein-Barr virus. I. Sequential occurrence from the virus-determined nuclear antigen synthesis, to blastogenesis, to DNA synthesis. Intervirology. 1979;11(1):30–39. doi: 10.1159/000149009. [DOI] [PubMed] [Google Scholar]
  21. Tokunaga M., Uemura Y., Tokudome T., Sato E. Epstein-Barr virus-infected T cells in infectious mononucleosis. Acta Pathol Jpn. 1993 Mar;43(3):146–147. doi: 10.1111/j.1440-1827.1993.tb01124.x. [DOI] [PubMed] [Google Scholar]
  22. Uchiyama T., Yodoi J., Sagawa K., Takatsuki K., Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481–492. [PubMed] [Google Scholar]
  23. Weiss L. M., Gaffey M. J., Chen Y. Y., Frierson H. F., Jr Frequency of Epstein-Barr viral DNA in "Western" sinonasal and Waldeyer's ring non-Hodgkin's lymphomas. Am J Surg Pathol. 1992 Feb;16(2):156–162. doi: 10.1097/00000478-199202000-00008. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Young L. S., Dawson C. W., Clark D., Rupani H., Busson P., Tursz T., Johnson A., Rickinson A. B. Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol. 1988 May;69(Pt 5):1051–1065. doi: 10.1099/0022-1317-69-5-1051. [DOI] [PubMed] [Google Scholar]
  26. 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]

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