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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2001 Apr 29;356(1408):461–473. doi: 10.1098/rstb.2000.0783

Biology and disease associations of Epstein-Barr virus.

D H Crawford 1
PMCID: PMC1088438  PMID: 11313005

Abstract

Epstein-Barr virus (EBV) is a human herpesvirus which infects almost all of the world's population subclinically during childhood and thereafter remains in the body for life. The virus colonizes antibody-producing (B) cells, which, as relatively long-lived resting cells, are an ideal site for long-term residence. Here EBV evades recognition and destruction by cytotoxic T cells. EBV is passed to naive hosts in saliva, but how the virus gains access to this route of transmission is not entirely clear. EBV carries a set of latent genes that, when expressed in resting B cells, induce cell proliferation and thereby increase the chances of successful virus colonization of the B-cell system during primary infection and the establishment of persistence. However, if this cell proliferation is not controlled, or if it is accompanied by additional genetic events within the infected cell, it can lead to malignancy. Thus EBV acts as a step in the evolution of an ever-increasing list of malignancies which are broadly of lymphoid or epithelial cell origin. In some of these, such as B-lymphoproliferative disease in the immunocompromised host, the role of the virus is central and well defined; in others, such as Burkitt's lymphoma, essential cofactors have been identified which act in concert with EBV in the evolution of the malignant clone. However, in several diseases in which the presence of EBV has more recently been discovered, the role of the virus is unclear. This review describes recent views on the EBV life cycle and its interlinks with normal B-cell biology, and discusses how this interrelationship may be upset and result in EBV-associated disease.

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Selected References

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  1. Anagnostopoulos I., Hummel M., Kreschel C., Stein H. Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood. 1995 Feb 1;85(3):744–750. [PubMed] [Google Scholar]
  2. Ansell J. D., Bancroft G. J. The biology of the SCID mutation. Immunol Today. 1989 Oct;10(10):322–325. doi: 10.1016/0167-5699(89)90181-3. [DOI] [PubMed] [Google Scholar]
  3. Armitage J. M., Kormos R. L., Stuart R. S., Fricker F. J., Griffith B. P., Nalesnik M., Hardesty R. L., Dummer J. S. Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant. 1991 Nov-Dec;10(6):877–887. [PubMed] [Google Scholar]
  4. Armstrong R. W., Imrey P. B., Lye M. S., Armstrong M. J., Yu M. C., Sani S. Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary exposures. Int J Cancer. 1998 Jul 17;77(2):228–235. doi: 10.1002/(sici)1097-0215(19980717)77:2<228::aid-ijc11>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  5. BURKITT D. A sarcoma involving the jaws in African children. Br J Surg. 1958 Nov;46(197):218–223. doi: 10.1002/bjs.18004619704. [DOI] [PubMed] [Google Scholar]
  6. Babcock G. J., Decker L. L., Freeman R. B., Thorley-Lawson D. A. Epstein-barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients. J Exp Med. 1999 Aug 16;190(4):567–576. doi: 10.1084/jem.190.4.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brooks L., Yao Q. Y., Rickinson A. B., Young L. S. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol. 1992 May;66(5):2689–2697. doi: 10.1128/jvi.66.5.2689-2697.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burkitt D. P. Etiology of Burkitt's lymphoma--an alternative hypothesis to a vectored virus. J Natl Cancer Inst. 1969 Jan;42(1):19–28. [PubMed] [Google Scholar]
  9. Callan M. F., Steven N., Krausa P., Wilson J. D., Moss P. A., Gillespie G. M., Bell J. I., Rickinson A. B., McMichael A. J. Large clonal expansions of CD8+ T cells in acute infectious mononucleosis. Nat Med. 1996 Aug;2(8):906–911. doi: 10.1038/nm0896-906. [DOI] [PubMed] [Google Scholar]
  10. Callan M. F., Tan L., Annels N., Ogg G. S., Wilson J. D., O'Callaghan C. A., Steven N., McMichael A. J., Rickinson A. B. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. J Exp Med. 1998 May 4;187(9):1395–1402. doi: 10.1084/jem.187.9.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cen H., Williams P. A., McWilliams H. P., Breinig M. C., Ho M., McKnight J. L. Evidence for restricted Epstein-Barr virus latent gene expression and anti-EBNA antibody response in solid organ transplant recipients with posttransplant lymphoproliferative disorders. Blood. 1993 Mar 1;81(5):1393–1403. [PubMed] [Google Scholar]
  12. Chen F., Zou J. Z., di Renzo L., Winberg G., Hu L. F., Klein E., Klein G., Ernberg I. 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. J Virol. 1995 Jun;69(6):3752–3758. doi: 10.1128/jvi.69.6.3752-3758.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chen H., Smith P., Ambinder R. F., Hayward S. D. Expression of Epstein-Barr virus BamHI-A rightward transcripts in latently infected B cells from peripheral blood. Blood. 1999 May 1;93(9):3026–3032. [PubMed] [Google Scholar]
  14. Cook R. C., Connors J. M., Gascoyne R. D., Fradet G., Levy R. D. Treatment of post-transplant lymphoproliferative disease with rituximab monoclonal antibody after lung transplantation. Lancet. 1999 Nov 13;354(9191):1698–1699. doi: 10.1016/S0140-6736(99)02058-9. [DOI] [PubMed] [Google Scholar]
  15. Crawford D. H., Ando I. EB virus induction is associated with B-cell maturation. Immunology. 1986 Nov;59(3):405–409. [PMC free article] [PubMed] [Google Scholar]
  16. Crawford D. H., Thomas J. A., Janossy G., Sweny P., Fernando O. N., Moorhead J. F., Thompson J. H. Epstein Barr virus nuclear antigen positive lymphoma after cyclosporin A treatment in patient with renal allograft. Lancet. 1980 Jun 21;1(8182):1355–1356. doi: 10.1016/s0140-6736(80)91800-0. [DOI] [PubMed] [Google Scholar]
  17. Dawson C. W., Rickinson A. B., Young L. S. Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 1990 Apr 19;344(6268):777–780. doi: 10.1038/344777a0. [DOI] [PubMed] [Google Scholar]
  18. Delecluse H. J., Bartnizke S., Hammerschmidt W., Bullerdiek J., Bornkamm G. W. Episomal and integrated copies of Epstein-Barr virus coexist in Burkitt lymphoma cell lines. J Virol. 1993 Mar;67(3):1292–1299. doi: 10.1128/jvi.67.3.1292-1299.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Farrell P. J., Allan G. J., Shanahan F., Vousden K. H., Crook T. p53 is frequently mutated in Burkitt's lymphoma cell lines. EMBO J. 1991 Oct;10(10):2879–2887. doi: 10.1002/j.1460-2075.1991.tb07837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Faulkner G. C., Burrows S. R., Khanna R., Moss D. J., Bird A. G., Crawford D. H. X-Linked agammaglobulinemia patients are not infected with Epstein-Barr virus: implications for the biology of the virus. J Virol. 1999 Feb;73(2):1555–1564. doi: 10.1128/jvi.73.2.1555-1564.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Faulkner G. C., Krajewski A. S., Crawford D. H. The ins and outs of EBV infection. Trends Microbiol. 2000 Apr;8(4):185–189. doi: 10.1016/s0966-842x(00)01742-x. [DOI] [PubMed] [Google Scholar]
  23. Fingeroth J. D., Clabby M. L., Strominger J. D. Characterization of a T-lymphocyte Epstein-Barr virus/C3d receptor (CD21). J Virol. 1988 Apr;62(4):1442–1447. doi: 10.1128/jvi.62.4.1442-1447.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Fischer A., Blanche S., Le Bidois J., Bordigoni P., Garnier J. L., Niaudet P., Morinet F., Le Deist F., Fischer A. M., Griscelli C. Anti-B-cell monoclonal antibodies in the treatment of severe B-cell lymphoproliferative syndrome following bone marrow and organ transplantation. N Engl J Med. 1991 May 23;324(21):1451–1456. doi: 10.1056/NEJM199105233242102. [DOI] [PubMed] [Google Scholar]
  25. Foss H. D., Herbst H., Hummel M., Araujo I., Latza U., Rancsò C., Dallenbach F., Stein H. Patterns of cytokine gene expression in infectious mononucleosis. Blood. 1994 Feb 1;83(3):707–712. [PubMed] [Google Scholar]
  26. Greenspan J. S., Greenspan D., Lennette E. T., Abrams D. I., Conant M. A., Petersen V., Freese U. K. Replication of Epstein-Barr virus within the epithelial cells of oral "hairy" leukoplakia, an AIDS-associated lesion. N Engl J Med. 1985 Dec 19;313(25):1564–1571. doi: 10.1056/NEJM198512193132502. [DOI] [PubMed] [Google Scholar]
  27. Greenwood B. M., Vick R. M. Evidence for a malaria mitogen in human malaria. Nature. 1975 Oct 16;257(5527):592–594. doi: 10.1038/257592a0. [DOI] [PubMed] [Google Scholar]
  28. Gutensohn N., Cole P. Epidemiology of Hodgkin's disease. Semin Oncol. 1980 Jun;7(2):92–102. [PubMed] [Google Scholar]
  29. Haque T., Thomas J. A., Falk K. I., Parratt R., Hunt B. J., Yacoub M., Crawford D. H. Transmission of donor Epstein-Barr virus (EBV) in transplanted organs causes lymphoproliferative disease in EBV-seronegative recipients. J Gen Virol. 1996 Jun;77(Pt 6):1169–1172. doi: 10.1099/0022-1317-77-6-1169. [DOI] [PubMed] [Google Scholar]
  30. Haque T., Thomas J. A., Parratt R., Hunt B. J., Yacoub M. H., Crawford D. H. A prospective study in heart and lung transplant recipients correlating persistent Epstein-Barr virus infection with clinical events. Transplantation. 1997 Oct 15;64(7):1028–1034. doi: 10.1097/00007890-199710150-00015. [DOI] [PubMed] [Google Scholar]
  31. Hopwood P., Crawford D. H. The role of EBV in post-transplant malignancies: a review. J Clin Pathol. 2000 Apr;53(4):248–254. doi: 10.1136/jcp.53.4.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Howie D., Sayos J., Terhorst C., Morra M. The gene defective in X-linked lymphoproliferative disease controls T cell dependent immune surveillance against Epstein-Barr virus. Curr Opin Immunol. 2000 Aug;12(4):474–478. doi: 10.1016/s0952-7915(00)00123-0. [DOI] [PubMed] [Google Scholar]
  33. Hunt B. J., Thomas J. A., Burke M., Walker H., Yacoub M., Crawford D. H. Epstein-Barr virus associated Burkitt lymphoma in a heart transplant recipient. Transplantation. 1996 Sep 27;62(6):869–872. doi: 10.1097/00007890-199609270-00030. [DOI] [PubMed] [Google Scholar]
  34. Imai S., Koizumi S., Sugiura M., Tokunaga M., Uemura Y., Yamamoto N., Tanaka S., Sato E., Osato T. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9131–9135. doi: 10.1073/pnas.91.19.9131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Israele V., Shirley P., Sixbey J. W. Excretion of the Epstein-Barr virus from the genital tract of men. J Infect Dis. 1991 Jun;163(6):1341–1343. doi: 10.1093/infdis/163.6.1341. [DOI] [PubMed] [Google Scholar]
  36. Johannessen I., Asghar M., Crawford D. H. Essential role for T cells in human B-cell lymphoproliferative disease development in severe combined immunodeficient mice. Br J Haematol. 2000 Jun;109(3):600–610. doi: 10.1046/j.1365-2141.2000.02066.x. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Karajannis M. A., Hummel M., Anagnostopoulos I., Stein H. Strict lymphotropism of Epstein-Barr virus during acute infectious mononucleosis in nonimmunocompromised individuals. Blood. 1997 Apr 15;89(8):2856–2862. [PubMed] [Google Scholar]
  39. Komano J., Maruo S., Kurozumi K., Oda T., Takada K. Oncogenic role of Epstein-Barr virus-encoded RNAs in Burkitt's lymphoma cell line Akata. J Virol. 1999 Dec;73(12):9827–9831. doi: 10.1128/jvi.73.12.9827-9831.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lam K. M., Syed N., Whittle H., Crawford D. H. Circulating Epstein-Barr virus-carrying B cells in acute malaria. Lancet. 1991 Apr 13;337(8746):876–878. doi: 10.1016/0140-6736(91)90203-2. [DOI] [PubMed] [Google Scholar]
  41. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  42. Levitskaya J., Coram M., Levitsky V., Imreh S., Steigerwald-Mullen P. M., Klein G., Kurilla M. G., Masucci M. G. Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature. 1995 Jun 22;375(6533):685–688. doi: 10.1038/375685a0. [DOI] [PubMed] [Google Scholar]
  43. Lu S. J., Day N. E., Degos L., Lepage V., Wang P. C., Chan S. H., Simons M., McKnight B., Easton D., Zeng Y. Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region. Nature. 1990 Aug 2;346(6283):470–471. doi: 10.1038/346470a0. [DOI] [PubMed] [Google Scholar]
  44. MacLennan I. C. Germinal centers. Annu Rev Immunol. 1994;12:117–139. doi: 10.1146/annurev.iy.12.040194.001001. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Magrath I. The pathogenesis of Burkitt's lymphoma. Adv Cancer Res. 1990;55:133–270. doi: 10.1016/s0065-230x(08)60470-4. [DOI] [PubMed] [Google Scholar]
  47. Martel-Renoir D., Grunewald V., Touitou R., Schwaab G., Joab I. Qualitative analysis of the expression of Epstein-Barr virus lytic genes in nasopharyngeal carcinoma biopsies. J Gen Virol. 1995 Jun;76(Pt 6):1401–1408. doi: 10.1099/0022-1317-76-6-1401. [DOI] [PubMed] [Google Scholar]
  48. Miyashita E. M., Yang B., Babcock G. J., Thorley-Lawson D. A. Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell. J Virol. 1997 Jul;71(7):4882–4891. doi: 10.1128/jvi.71.7.4882-4891.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Miyashita E. M., Yang B., Lam K. M., Crawford D. H., Thorley-Lawson D. A. A novel form of Epstein-Barr virus latency in normal B cells in vivo. Cell. 1995 Feb 24;80(4):593–601. doi: 10.1016/0092-8674(95)90513-8. [DOI] [PubMed] [Google Scholar]
  50. Mosier D. E., Gulizia R. J., Baird S. M., Wilson D. B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988 Sep 15;335(6187):256–259. doi: 10.1038/335256a0. [DOI] [PubMed] [Google Scholar]
  51. Mueller N., Evans A., Harris N. L., Comstock G. W., Jellum E., Magnus K., Orentreich N., Polk B. F., Vogelman J. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med. 1989 Mar 16;320(11):689–695. doi: 10.1056/NEJM198903163201103. [DOI] [PubMed] [Google Scholar]
  52. Nicholson L. J., Hopwood P., Johannessen I., Salisbury J. R., Codd J., Thorley-Lawson D., Crawford D. H. Epstein-Barr virus latent membrane protein does not inhibit differentiation and induces tumorigenicity of human epithelial cells. Oncogene. 1997 Jul 17;15(3):275–283. doi: 10.1038/sj.onc.1201187. [DOI] [PubMed] [Google Scholar]
  53. Old L. J., Boyse E. A., Oettgen H. F., Harven E. D., Geering G., Williamson B., Clifford P. Precipitating antibody in human serum to an antigen present in cultured burkitt's lymphoma cells. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1699–1704. doi: 10.1073/pnas.56.6.1699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Oudejans J. J., Jiwa M., van den Brule A. J., Grässer F. A., Horstman A., Vos W., Kluin P. M., van der Valk P., Walboomers J. M., Meijer C. J. Detection of heterogeneous Epstein-Barr virus gene expression patterns within individual post-transplantation lymphoproliferative disorders. Am J Pathol. 1995 Oct;147(4):923–933. [PMC free article] [PubMed] [Google Scholar]
  55. 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]
  56. Perera S. M., Thomas J. A., Burke M., Crawford D. H. Analysis of the T-cell micro-environment in Epstein-Barr virus-related post-transplantation B lymphoproliferative disease. J Pathol. 1998 Feb;184(2):177–184. doi: 10.1002/(SICI)1096-9896(199802)184:2<177::AID-PATH977>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  57. Pope J. H., Horne M. K., Scott W. Transformation of foetal human keukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int J Cancer. 1968 Nov 15;3(6):857–866. doi: 10.1002/ijc.2910030619. [DOI] [PubMed] [Google Scholar]
  58. 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]
  59. Raab-Traub N. Epstein-Barr virus and nasopharyngeal carcinoma. Semin Cancer Biol. 1992 Oct;3(5):297–307. [PubMed] [Google Scholar]
  60. Raab-Traub N., Flynn K., Pearson G., Huang A., Levine P., Lanier A., Pagano J. The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA. Int J Cancer. 1987 Jan 15;39(1):25–29. doi: 10.1002/ijc.2910390106. [DOI] [PubMed] [Google Scholar]
  61. 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]
  62. Rickinson A. B., Callan M. F., Annels N. E. T-cell memory: lessons from Epstein-Barr virus infection in man. Philos Trans R Soc Lond B Biol Sci. 2000 Mar 29;355(1395):391–400. doi: 10.1098/rstb.2000.0579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Rooney C. M., Smith C. A., Ng C. Y., Loftin S., Li C., Krance R. A., Brenner M. K., Heslop H. E. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995 Jan 7;345(8941):9–13. doi: 10.1016/s0140-6736(95)91150-2. [DOI] [PubMed] [Google Scholar]
  64. 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]
  65. Sayos J., Wu C., Morra M., Wang N., Zhang X., Allen D., van Schaik S., Notarangelo L., Geha R., Roncarolo M. G. The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM. Nature. 1998 Oct 1;395(6701):462–469. doi: 10.1038/26683. [DOI] [PubMed] [Google Scholar]
  66. Sixbey J. W., Lemon S. M., Pagano J. S. A second site for Epstein-Barr virus shedding: the uterine cervix. Lancet. 1986 Nov 15;2(8516):1122–1124. doi: 10.1016/s0140-6736(86)90531-3. [DOI] [PubMed] [Google Scholar]
  67. Srinivas S. K., Sixbey J. W. Epstein-Barr virus induction of recombinase-activating genes RAG1 and RAG2. J Virol. 1995 Dec;69(12):8155–8158. doi: 10.1128/jvi.69.12.8155-8158.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Starzl T. E., Nalesnik M. A., Porter K. A., Ho M., Iwatsuki S., Griffith B. P., Rosenthal J. T., Hakala T. R., Shaw B. W., Jr, Hardesty R. L. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet. 1984 Mar 17;1(8377):583–587. doi: 10.1016/s0140-6736(84)90994-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sutkowski N., Palkama T., Ciurli C., Sekaly R. P., Thorley-Lawson D. A., Huber B. T. An Epstein-Barr virus-associated superantigen. J Exp Med. 1996 Sep 1;184(3):971–980. doi: 10.1084/jem.184.3.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Thomas J. A., Allday M. J., Crawford D. H. Epstein-Barr virus-associated lymphoproliferative disorders in immunocompromised individuals. Adv Cancer Res. 1991;57:329–380. doi: 10.1016/s0065-230x(08)61003-9. [DOI] [PubMed] [Google Scholar]
  71. Thomas J. A., Felix D. H., Wray D., Southam J. C., Cubie H. A., Crawford D. H. Epstein-Barr virus gene expression and epithelial cell differentiation in oral hairy leukoplakia. Am J Pathol. 1991 Dec;139(6):1369–1380. [PMC free article] [PubMed] [Google Scholar]
  72. Thomas J. A., Hotchin N. A., Allday M. J., Amlot P., Rose M., Yacoub M., Crawford D. H. Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals. Transplantation. 1990 May;49(5):944–953. doi: 10.1097/00007890-199005000-00022. [DOI] [PubMed] [Google Scholar]
  73. Thorley-Lawson D. A., Babcock G. J. A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells. Life Sci. 1999;65(14):1433–1453. doi: 10.1016/s0024-3205(99)00214-3. [DOI] [PubMed] [Google Scholar]
  74. Tierney R. J., Steven N., Young L. S., Rickinson A. B. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J Virol. 1994 Nov;68(11):7374–7385. doi: 10.1128/jvi.68.11.7374-7385.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. 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]
  76. Weiss L. M., Strickler J. G., Warnke R. A., Purtilo D. T., Sklar J. Epstein-Barr viral DNA in tissues of Hodgkin's disease. Am J Pathol. 1987 Oct;129(1):86–91. [PMC free article] [PubMed] [Google Scholar]
  77. Whittle H. C., Brown J., Marsh K., Greenwood B. M., Seidelin P., Tighe H., Wedderburn L. T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria. 1984 Nov 29-Dec 5Nature. 312(5993):449–450. doi: 10.1038/312449a0. [DOI] [PubMed] [Google Scholar]
  78. Wilson J. B., Bell J. L., Levine A. J. Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice. EMBO J. 1996 Jun 17;15(12):3117–3126. [PMC free article] [PubMed] [Google Scholar]
  79. Wolf H., zur Hausen H., Becker V. EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nat New Biol. 1973 Aug 22;244(138):245–247. doi: 10.1038/newbio244245a0. [DOI] [PubMed] [Google Scholar]
  80. Wu T. C., Mann R. B., Charache P., Hayward S. D., Staal S., Lambe B. C., Ambinder R. F. Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease. Int J Cancer. 1990 Nov 15;46(5):801–804. doi: 10.1002/ijc.2910460509. [DOI] [PubMed] [Google Scholar]
  81. 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]
  82. Young L. S., Dawson C. W., Brown K. W., Rickinson A. B. Identification of a human epithelial cell surface protein sharing an epitope with the C3d/Epstein-Barr virus receptor molecule of B lymphocytes. Int J Cancer. 1989 May 15;43(5):786–794. doi: 10.1002/ijc.2910430508. [DOI] [PubMed] [Google Scholar]
  83. Zech L., Haglund U., Nilsson K., Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer. 1976 Jan 15;17(1):47–56. doi: 10.1002/ijc.2910170108. [DOI] [PubMed] [Google Scholar]
  84. Ziegler J. L., Drew W. L., Miner R. C., Mintz L., Rosenbaum E., Gershow J., Lennette E. T., Greenspan J., Shillitoe E., Beckstead J. Outbreak of Burkitt's-like lymphoma in homosexual men. Lancet. 1982 Sep 18;2(8299):631–633. doi: 10.1016/s0140-6736(82)92740-4. [DOI] [PubMed] [Google Scholar]

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