Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Aug;145(2):239–252.

Detection and characterization of Epstein-Barr virus in clinical specimens.

R F Ambinder 1, R B Mann 1
PMCID: PMC1887400  PMID: 8053485

Abstract

Epstein-Barr virus (EBV) is associated with a wide spectrum of benign and malignant diseases. Recent additions to the list include oral hairy leukoplakia; a subset of Hodgkin's lymphomas, particularly those with mixed cellularity histology or those occurring in underdeveloped countries; a subset of diffuse large cell/immunoblastic lymphoma in the immunocompromised, particularly primary central nervous system lymphoma; a subset of peripheral T cell lymphomas; and a subset of gastric carcinomas, particularly undifferentiated carcinomas. There are several distinctive aspects of the biology of the virus that are important in investigations of virus in clinical specimens. The presence of repeated elements in the genome facilitates detection of viral nucleic acids by a variety of hybridization techniques as well as the characterization of the clonality of virus-infected tissues. Latent viral infection is associated with several different patterns of viral gene expression in infected cells. Latent gene products are important because of their growth-regulating and -transforming properties as well as the potent cytotoxic T cell response they elicit. The abundant expression of the EBER RNA transcripts makes possible the sensitive detection of latent infection in EBV-associated tumors. Lytic infection can be inhibited by antiviral nucleoside analogues. Two lytic gene products are of special interest because of their homology to the cellular proteins BCL-2 and interleukin-10. Two viral biotypes or strains with different properties in terms of lymphocyte immortalization and transformation have recently been characterized. Current evidence suggests a differential biotype association with particular malignancies. Characterization of the association of EBV with various disease processes promises to be important for diagnosis and treatment as well as for a better understanding of the epidemiology and pathogenesis of these diabetes.

Full text

PDF
241

Images in this article

245Figure 3
on p.245
246Figure 4
on p.246
247Figure 5
on p.247

Selected References

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

  1. Ambinder R. F., Browning P. J., Lorenzana I., Leventhal B. G., Cosenza H., Mann R. B., MacMahon E. M., Medina R., Cardona V., Grufferman S. Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States. Blood. 1993 Jan 15;81(2):462–467. [PubMed] [Google Scholar]
  2. Ambinder R. F., Lambe B. C., Mann R. B., Hayward S. D., Zehnbauer B. A., Burns W. S., Charache P. Oligonucleotides for polymerase chain reaction amplification and hybridization detection of Epstein-Barr virus DNA in clinical specimens. Mol Cell Probes. 1990 Oct;4(5):397–407. doi: 10.1016/0890-8508(90)90030-4. [DOI] [PubMed] [Google Scholar]
  3. Anagnostopoulos I., Herbst H., Niedobitek G., Stein H. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood. 1989 Aug 1;74(2):810–816. [PubMed] [Google Scholar]
  4. Anagnostopoulos I., Hummel M., Finn T., Tiemann M., Korbjuhn P., Dimmler C., Gatter K., Dallenbach F., Parwaresch M. R., Stein H. Heterogeneous Epstein-Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type. Blood. 1992 Oct 1;80(7):1804–1812. [PubMed] [Google Scholar]
  5. Barletta J. M., Kingma D. W., Ling Y., Charache P., Mann R. B., Ambinder R. F. Rapid in situ hybridization for the diagnosis of latent Epstein-Barr virus infection. Mol Cell Probes. 1993 Apr;7(2):105–109. doi: 10.1006/mcpr.1993.1014. [DOI] [PubMed] [Google Scholar]
  6. Bashir R. M., Harris N. L., Hochberg F. H., Singer R. M. Detection of Epstein-Barr virus in CNS lymphomas by in-situ hybridization. Neurology. 1989 Jun;39(6):813–817. doi: 10.1212/wnl.39.6.813. [DOI] [PubMed] [Google Scholar]
  7. Bashir R., Hochberg F., Singer R. H. Detection of Epstein-Barr virus by in situ hybridization. Progress toward development of a nonisotopic diagnostic test. Am J Pathol. 1989 Dec;135(6):1035–1044. [PMC free article] [PubMed] [Google Scholar]
  8. Borisch B., Hennig I., Laeng R. H., Waelti E. R., Kraft R., Laissue J. Association of the subtype 2 of the Epstein-Barr virus with T-cell non-Hodgkin's lymphoma of the midline granuloma type. Blood. 1993 Aug 1;82(3):858–864. [PubMed] [Google Scholar]
  9. Bourgault I., Gomez A., Gomard E., Levy J. P. Limiting-dilution analysis of the HLA restriction of anti-Epstein-Barr virus-specific cytolytic T lymphocytes. Clin Exp Immunol. 1991 Jun;84(3):501–507. [PMC free article] [PubMed] [Google Scholar]
  10. Boyle M. J., Vasak E., Tschuchnigg M., Turner J. J., Sculley T., Penny R., Cooper D. A., Tindall B., Sewell W. A. Subtypes of Epstein-Barr virus (EBV) in Hodgkin's disease: association between B-type EBV and immunocompromise. Blood. 1993 Jan 15;81(2):468–474. [PubMed] [Google Scholar]
  11. 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]
  12. Brousset P., Knecht H., Rubin B., Drouet E., Chittal S., Meggetto F., Saati T. A., Bachmann E., Denoyel G., Sergeant A. Demonstration of Epstein-Barr virus replication in Reed-Sternberg cells of Hodgkin's disease. Blood. 1993 Aug 1;82(3):872–876. [PubMed] [Google Scholar]
  13. Busson P., McCoy R., Sadler R., Gilligan K., Tursz T., Raab-Traub N. Consistent transcription of the Epstein-Barr virus LMP2 gene in nasopharyngeal carcinoma. J Virol. 1992 May;66(5):3257–3262. doi: 10.1128/jvi.66.5.3257-3262.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Carmichael A., Jin X., Sissons P., Borysiewicz L. Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease. J Exp Med. 1993 Feb 1;177(2):249–256. doi: 10.1084/jem.177.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cen H., Breinig M. C., Atchison R. W., Ho M., McKnight J. L. Epstein-Barr virus transmission via the donor organs in solid organ transplantation: polymerase chain reaction and restriction fragment length polymorphism analysis of IR2, IR3, and IR4. J Virol. 1991 Feb;65(2):976–980. doi: 10.1128/jvi.65.2.976-980.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Chang K. L., Albújar P. F., Chen Y. Y., Johnson R. M., Weiss L. M. High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin's disease occurring in Peru. Blood. 1993 Jan 15;81(2):496–501. [PubMed] [Google Scholar]
  18. Chen C. L., Sadler R. H., Walling D. M., Su I. J., Hsieh H. C., Raab-Traub N. Epstein-Barr virus (EBV) gene expression in EBV-positive peripheral T-cell lymphomas. J Virol. 1993 Oct;67(10):6303–6308. doi: 10.1128/jvi.67.10.6303-6308.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Chen M. R., Middeldorp J. M., Hayward S. D. Separation of the complex DNA binding domain of EBNA-1 into DNA recognition and dimerization subdomains of novel structure. J Virol. 1993 Aug;67(8):4875–4885. doi: 10.1128/jvi.67.8.4875-4885.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Chen X. Y., Pepper S. D., Arrand J. R. Prevalence of the A and B types of Epstein-Barr virus DNA in nasopharyngeal carcinoma biopsies from southern China. J Gen Virol. 1992 Feb;73(Pt 2):463–466. doi: 10.1099/0022-1317-73-2-463. [DOI] [PubMed] [Google Scholar]
  21. Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
  22. Cohen J. I., Picchio G. R., Mosier D. E. Epstein-Barr virus nuclear protein 2 is a critical determinant for tumor growth in SCID mice and for transformation in vitro. J Virol. 1992 Dec;66(12):7555–7559. doi: 10.1128/jvi.66.12.7555-7559.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. De Re V., Boiocchi M., De Vita S., Dolcetti R., Gloghini A., Uccini S., Baroni C., Scarpa A., Cattoretti G., Carbone A. Subtypes of Epstein-Barr virus in HIV-1-associated and HIV-1-unrelated Hodgkin's disease cases. Int J Cancer. 1993 Jul 30;54(6):895–898. doi: 10.1002/ijc.2910540603. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Delsol G., Brousset P., Chittal S., Rigal-Huguet F. Correlation of the expression of Epstein-Barr virus latent membrane protein and in situ hybridization with biotinylated BamHI-W probes in Hodgkin's disease. Am J Pathol. 1992 Feb;140(2):247–253. [PMC free article] [PubMed] [Google Scholar]
  26. Delsol G., Meggetto F., Brousset P., Cohen-Knafo E., al Saati T., Rochaix P., Gorguet B., Rubin B., Voigt J. J., Chittal S. Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen. Am J Pathol. 1993 Jun;142(6):1729–1738. [PMC free article] [PubMed] [Google Scholar]
  27. Gilligan K., Rajadurai P., Resnick L., Raab-Traub N. Epstein-Barr virus small nuclear RNAs are not expressed in permissively infected cells in AIDS-associated leukoplakia. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8790–8794. doi: 10.1073/pnas.87.22.8790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Gledhill S., Gallagher A., Jones D. B., Krajewski A. S., Alexander F. E., Klee E., Wright D. H., O'Brien C., Onions D. E., Jarrett R. F. Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples. Br J Cancer. 1991 Aug;64(2):227–232. doi: 10.1038/bjc.1991.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Glickman J. N., Howe J. G., Steitz J. A. Structural analyses of EBER1 and EBER2 ribonucleoprotein particles present in Epstein-Barr virus-infected cells. J Virol. 1988 Mar;62(3):902–911. doi: 10.1128/jvi.62.3.902-911.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Gratama J. W., Oosterveer M. A., Klein G., Ernberg I. EBNA size polymorphism can be used to trace Epstein-Barr virus spread within families. J Virol. 1990 Oct;64(10):4703–4708. doi: 10.1128/jvi.64.10.4703-4708.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Gulley M. L., Raphael M., Lutz C. T., Ross D. W., Raab-Traub N. Epstein-Barr virus integration in human lymphomas and lymphoid cell lines. Cancer. 1992 Jul 1;70(1):185–191. doi: 10.1002/1097-0142(19920701)70:1<185::aid-cncr2820700129>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  32. Gutierrez M. I., Bhatia K., Magrath I. Replicative viral DNA in Epstein-Barr virus associated Burkitt's lymphoma biopsies. Leuk Res. 1993 Mar;17(3):285–289. doi: 10.1016/0145-2126(93)90013-b. [DOI] [PubMed] [Google Scholar]
  33. Hamilton-Dutoit S. J., Pallesen G., Franzmann M. B., Karkov J., Black F., Skinhøj P., Pedersen C. AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. Am J Pathol. 1991 Jan;138(1):149–163. [PMC free article] [PubMed] [Google Scholar]
  34. Hamilton-Dutoit S. J., Rea D., Raphael M., Sandvej K., Delecluse H. J., Gisselbrecht C., Marelle L., van Krieken H. J., Pallesen G. Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency. Am J Pathol. 1993 Oct;143(4):1072–1085. [PMC free article] [PubMed] [Google Scholar]
  35. Hamilton-Dutoit S. J., Therkildsen M. H., Neilsen N. H., Jensen H., Hansen J. P., Pallesen G. Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of Epstein-Barr virus DNA by in situ nucleic acid hybridization. Hum Pathol. 1991 Aug;22(8):811–815. doi: 10.1016/0046-8177(91)90210-g. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991 Jun 28;65(7):1107–1115. doi: 10.1016/0092-8674(91)90007-l. [DOI] [PubMed] [Google Scholar]
  38. Herbst H., Dallenbach F., Hummel M., Niedobitek G., Pileri S., Müller-Lantzsch N., Stein H. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4766–4770. doi: 10.1073/pnas.88.11.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Herbst H., Niedobitek G., Kneba M., Hummel M., Finn T., Anagnostopoulos I., Bergholz M., Krieger G., Stein H. High incidence of Epstein-Barr virus genomes in Hodgkin's disease. Am J Pathol. 1990 Jul;137(1):13–18. [PMC free article] [PubMed] [Google Scholar]
  40. Herbst H., Steinbrecher E., Niedobitek G., Young L. S., Brooks L., Müller-Lantzsch N., Stein H. Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease. Blood. 1992 Jul 15;80(2):484–491. [PubMed] [Google Scholar]
  41. Hitt M. M., Allday M. J., Hara T., Karran L., Jones M. D., Busson P., Tursz T., Ernberg I., Griffin B. E. EBV gene expression in an NPC-related tumour. EMBO J. 1989 Sep;8(9):2639–2651. doi: 10.1002/j.1460-2075.1989.tb08404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Howe J. G., Steitz J. A. Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9006–9010. doi: 10.1073/pnas.83.23.9006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Jain V. K., Judde J. G., Max E. E., Magrath I. T. Variable IgH chain enhancer activity in Burkitt's lymphomas suggests an additional, direct mechanism of c-myc deregulation. J Immunol. 1993 Jun 15;150(12):5418–5428. [PubMed] [Google Scholar]
  45. Jarrett R. F., Gallagher A., Jones D. B., Alexander F. E., Krajewski A. S., Kelsey A., Adams J., Angus B., Gledhill S., Wright D. H. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age. J Clin Pathol. 1991 Oct;44(10):844–848. doi: 10.1136/jcp.44.10.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Jiwa N. M., Kanavaros P., van der Valk P., Walboomers J. M., Horstman A., Vos W., Mullink H., Meijer C. J. Expression of c-myc and bcl-2 oncogene products in Reed-Sternberg cells independent of presence of Epstein-Barr virus. J Clin Pathol. 1993 Mar;46(3):211–217. doi: 10.1136/jcp.46.3.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. Kanavaros P., Lescs M. C., Brière J., Divine M., Galateau F., Joab I., Bosq J., Farcet J. P., Reyes F., Gaulard P. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood. 1993 May 15;81(10):2688–2695. [PubMed] [Google Scholar]
  49. Katz B. Z., Raab-Traub N., Miller G. Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases. J Infect Dis. 1989 Oct;160(4):589–598. doi: 10.1093/infdis/160.4.589. [DOI] [PubMed] [Google Scholar]
  50. Kawa-Ha K., Ishihara S., Ninomiya T., Yumura-Yagi K., Hara J., Murayama F., Tawa A., Hirai K. CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA. J Clin Invest. 1989 Jul;84(1):51–55. doi: 10.1172/JCI114168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Khan G., Coates P. J., Gupta R. K., Kangro H. O., Slavin G. Presence of Epstein-Barr virus in Hodgkin's disease is not exclusive to Reed-Sternberg cells. Am J Pathol. 1992 Apr;140(4):757–762. [PMC free article] [PubMed] [Google Scholar]
  52. Khan G., Norton A. J., Slavin G. Epstein-Barr virus in Hodgkin disease. Relation to age and subtype. Cancer. 1993 May 15;71(10):3124–3129. doi: 10.1002/1097-0142(19930515)71:10<3124::aid-cncr2820711038>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  53. Khanna R., Burrows S. R., Kurilla M. G., Jacob C. A., Misko I. S., Sculley T. B., Kieff E., Moss D. J. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. J Exp Med. 1992 Jul 1;176(1):169–176. doi: 10.1084/jem.176.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Kingma D. W., Medeiros L. J., Barletta J., Raffeld M., Mann R. B., Ambinder R. F., Jaffe E. S. Epstein-Barr virus is infrequently identified in non-Hodgkin's lymphomas associated with Hodgkin's disease. Am J Surg Pathol. 1994 Jan;18(1):48–61. doi: 10.1097/00000478-199401000-00005. [DOI] [PubMed] [Google Scholar]
  55. Knecht H., Bachmann E., Brousset P., Sandvej K., Nadal D., Bachmann F., Odermatt B. F., Delsol G., Pallesen G. Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin's disease and identical to those observed in nasopharyngeal carcinoma. Blood. 1993 Nov 15;82(10):2937–2942. [PubMed] [Google Scholar]
  56. Korbjuhn P., Anagnostopoulos I., Hummel M., Tiemann M., Dallenbach F., Parwaresch M. R., Stein H. Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas. Blood. 1993 Jul 1;82(1):217–223. [PubMed] [Google Scholar]
  57. Lee S. H., Su I. J., Chen R. L., Lin K. S., Lin D. T., Chuu W. M., Lin K. S. A pathologic study of childhood lymphoma in Taiwan with special reference to peripheral T-cell lymphoma and the association with Epstein-Barr viral infection. Cancer. 1991 Nov 1;68(9):1954–1962. doi: 10.1002/1097-0142(19911101)68:9<1954::aid-cncr2820680918>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  58. Lestou V. S., De Braekeleer M., Strehl S., Ott G., Gadner H., Ambros P. F. Non-random integration of Epstein-Barr virus in lymphoblastoid cell lines. Genes Chromosomes Cancer. 1993 Sep;8(1):38–48. doi: 10.1002/gcc.2870080108. [DOI] [PubMed] [Google Scholar]
  59. Ling P. D., Rawlins D. R., Hayward S. D. The Epstein-Barr virus immortalizing protein EBNA-2 is targeted to DNA by a cellular enhancer-binding protein. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9237–9241. doi: 10.1073/pnas.90.20.9237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Longnecker R., Kieff E. A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1. J Virol. 1990 May;64(5):2319–2326. doi: 10.1128/jvi.64.5.2319-2326.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Longnecker R., Miller C. L., Miao X. Q., Tomkinson B., Kieff E. The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein-Barr virus latent membrane protein 2 (LMP2) are dispensable for lymphocyte infection and growth transformation in vitro. J Virol. 1993 Apr;67(4):2006–2013. doi: 10.1128/jvi.67.4.2006-2013.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. 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]
  63. Mann R. B., Wu T. C., MacMahon E. M., Ling Y., Charache P., Ambinder R. F. In situ localization of Epstein-Barr virus in thymic carcinoma. Mod Pathol. 1992 Jul;5(4):363–366. [PubMed] [Google Scholar]
  64. Moore K. W., Vieira P., Fiorentino D. F., Trounstine M. L., Khan T. A., Mosmann T. R. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. doi: 10.1126/science.2161559. [DOI] [PubMed] [Google Scholar]
  65. Moorthy R. K., Thorley-Lawson D. A. Biochemical, genetic, and functional analyses of the phosphorylation sites on the Epstein-Barr virus-encoded oncogenic latent membrane protein LMP-1. J Virol. 1993 May;67(5):2637–2645. doi: 10.1128/jvi.67.5.2637-2645.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Murray P. G., Young L. S., Rowe M., Crocker J. Immunohistochemical demonstration of the Epstein-Barr virus-encoded latent membrane protein in paraffin sections of Hodgkin's disease. J Pathol. 1992 Jan;166(1):1–5. doi: 10.1002/path.1711660102. [DOI] [PubMed] [Google Scholar]
  67. Murray R. J., Kurilla M. G., Brooks J. M., Thomas W. A., Rowe M., Kieff E., Rickinson A. B. Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med. 1992 Jul 1;176(1):157–168. doi: 10.1084/jem.176.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Niedobitek G., Herbst H., Young L. S., Brooks L., Masucci M. G., Crocker J., Rickinson A. B., Stein H. Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue. Blood. 1992 May 15;79(10):2520–2526. [PubMed] [Google Scholar]
  69. Oda K., Tamaru J., Takenouchi T., Mikata A., Nunomura M., Saitoh N., Sarashina H., Nakajima N. Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma. Am J Pathol. 1993 Oct;143(4):1063–1071. [PMC free article] [PubMed] [Google Scholar]
  70. Packham G., Brimmell M., Cook D., Sinclair A. J., Farrell P. J. Strain variation in Epstein-Barr virus immediate early genes. Virology. 1993 Feb;192(2):541–550. doi: 10.1006/viro.1993.1070. [DOI] [PubMed] [Google Scholar]
  71. Pagano J. S. Pathogenesis and treatment of Epstein-Barr virus infection. J Exp Pathol. 1987 Summer;3(4):441–448. [PubMed] [Google Scholar]
  72. 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]
  73. Pallesen G., Sandvej K., Hamilton-Dutoit S. J., Rowe M., Young L. S. Activation of Epstein-Barr virus replication in Hodgkin and Reed-Sternberg cells. Blood. 1991 Sep 1;78(5):1162–1165. [PubMed] [Google Scholar]
  74. Poppema S., van Imhoff G., Torensma R., Smit J. Lymphadenopathy morphologically consistent with Hodgkin's disease associated with Epstein-Barr virus infection. Am J Clin Pathol. 1985 Sep;84(3):385–390. doi: 10.1093/ajcp/84.3.385. [DOI] [PubMed] [Google Scholar]
  75. 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]
  76. Raab-Traub N., Rajadurai P., Flynn K., Lanier A. P. Epstein-Barr virus infection in carcinoma of the salivary gland. J Virol. 1991 Dec;65(12):7032–7036. doi: 10.1128/jvi.65.12.7032-7036.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Rogers B. B., Alpert L. C., Hine E. A., Buffone G. J. Analysis of DNA in fresh and fixed tissue by the polymerase chain reaction. Am J Pathol. 1990 Mar;136(3):541–548. [PMC free article] [PubMed] [Google Scholar]
  78. 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]
  79. Rowe M., Young L. S., Crocker J., Stokes H., Henderson S., Rickinson A. B. Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man. J Exp Med. 1991 Jan 1;173(1):147–158. doi: 10.1084/jem.173.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Ryan C. A. Oligosaccharide signals: from plant defense to parasite offense. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):1–2. doi: 10.1073/pnas.91.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Ryon J. J., Hayward S. D., MacMahon E. M., Mann R. B., Ling Y., Charache P., Phelan J. A., Miller G., Ambinder R. F. In situ detection of lytic Epstein-Barr virus infection: expression of the NotI early gene and viral interleukin-10 late gene in clinical specimens. J Infect Dis. 1993 Aug;168(2):345–351. doi: 10.1093/infdis/168.2.345. [DOI] [PubMed] [Google Scholar]
  82. Sample J., Brooks L., Sample C., Young L., Rowe M., Gregory C., Rickinson A., Kieff E. Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr nuclear antigen 1 transcriptional initiation site. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6343–6347. doi: 10.1073/pnas.88.14.6343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Sample J., Young L., Martin B., Chatman T., Kieff E., Rickinson A., Kieff E. Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol. 1990 Sep;64(9):4084–4092. doi: 10.1128/jvi.64.9.4084-4092.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Sato H., Takimoto T., Tanaka S., Tanaka J., Raab-Traub N. Concatameric replication of Epstein-Barr virus: structure of the termini in virus-producer and newly transformed cell lines. J Virol. 1990 Nov;64(11):5295–5300. doi: 10.1128/jvi.64.11.5295-5300.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Schaefer B. C., Woisetschlaeger M., Strominger J. L., Speck S. H. 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. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6550–6554. doi: 10.1073/pnas.88.15.6550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Sculley T. B., Apolloni A., Hurren L., Moss D. J., Cooper D. A. Coinfection with A- and B-type Epstein-Barr virus in human immunodeficiency virus-positive subjects. J Infect Dis. 1990 Sep;162(3):643–648. doi: 10.1093/infdis/162.3.642. [DOI] [PubMed] [Google Scholar]
  87. 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]
  88. Shibata D., Weiss L. M., Hernandez A. M., Nathwani B. N., Bernstein L., Levine A. M. Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus. Blood. 1993 Apr 15;81(8):2102–2109. [PubMed] [Google Scholar]
  89. Shiramizu B., Barriga F., Neequaye J., Jafri A., Dalla-Favera R., Neri A., Guttierez M., Levine P., Magrath I. Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association. Blood. 1991 Apr 1;77(7):1516–1526. [PubMed] [Google Scholar]
  90. Sixbey J. W., Shirley P., Chesney P. J., Buntin D. M., Resnick L. Detection of a second widespread strain of Epstein-Barr virus. Lancet. 1989 Sep 30;2(8666):761–765. doi: 10.1016/s0140-6736(89)90829-5. [DOI] [PubMed] [Google Scholar]
  91. Sixbey J. W., Yao Q. Y. Immunoglobulin A-induced shift of Epstein-Barr virus tissue tropism. Science. 1992 Mar 20;255(5051):1578–1580. doi: 10.1126/science.1312750. [DOI] [PubMed] [Google Scholar]
  92. 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]
  93. 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]
  94. Subar M., Neri A., Inghirami G., Knowles D. M., Dalla-Favera R. Frequent c-myc oncogene activation and infrequent presence of Epstein-Barr virus genome in AIDS-associated lymphoma. Blood. 1988 Aug;72(2):667–671. [PubMed] [Google Scholar]
  95. Tokunaga M., Land C. E., Uemura Y., Tokudome T., Tanaka S., Sato E. Epstein-Barr virus in gastric carcinoma. Am J Pathol. 1993 Nov;143(5):1250–1254. [PMC free article] [PubMed] [Google Scholar]
  96. Weiss L. M., Chen Y. Y., Liu X. F., Shibata D. Epstein-Barr virus and Hodgkin's disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol. 1991 Dec;139(6):1259–1265. [PMC free article] [PubMed] [Google Scholar]
  97. Weiss L. M., Movahed L. A. In situ demonstration of Epstein-Barr viral genomes in viral-associated B cell lymphoproliferations. Am J Pathol. 1989 Mar;134(3):651–659. [PMC free article] [PubMed] [Google Scholar]
  98. 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]
  99. 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]
  100. Woisetschlaeger M., Yandava C. N., Furmanski L. A., Strominger J. L., Speck S. H. Promoter switching in Epstein-Barr virus during the initial stages of infection of B lymphocytes. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1725–1729. doi: 10.1073/pnas.87.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. 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]
  102. Wu T. C., Mann R. B., Epstein J. I., MacMahon E., Lee W. A., Charache P., Hayward S. D., Kurman R. J., Hayward G. S., Ambinder R. F. Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. Am J Pathol. 1991 Jun;138(6):1461–1469. [PMC free article] [PubMed] [Google Scholar]
  103. Young L. S., Lau R., Rowe M., Niedobitek G., Packham G., Shanahan F., Rowe D. T., Greenspan D., Greenspan J. S., Rickinson A. B. Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. J Virol. 1991 Jun;65(6):2868–2874. doi: 10.1128/jvi.65.6.2868-2874.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. 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]
  105. de Campos-Lima P. O., Gavioli R., Zhang Q. J., Wallace L. E., Dolcetti R., Rowe M., Rickinson A. B., Masucci M. G. HLA-A11 epitope loss isolates of Epstein-Barr virus from a highly A11+ population. Science. 1993 Apr 2;260(5104):98–100. doi: 10.1126/science.7682013. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES