1887

Abstract

Polymorphisms in Epstein–Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked ‘Wu’ or ‘Li’ alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele ‘Sp’ at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.

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2011-05-01
2020-01-20
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References

  1. Bhatia K. , Raj A. , Guitierrez M. I. , Judde J. G. , Spangler G. , Venkatesh H. , Magrath I. T. . ( 1996; ). Variation in the sequence of Epstein–Barr virus nuclear antigen 1 in normal peripheral blood lymphocytes and in Burkitt’s lymphomas. . Oncogene 13:, 177–181.[PubMed]
    [Google Scholar]
  2. Burrows S. R. , Gardner J. , Khanna R. , Steward T. , Moss D. J. , Rodda S. , Suhrbier A. . ( 1994; ). Five new cytotoxic T cell epitopes identified within Epstein–Barr virus nuclear antigen 3. . J Gen Virol 75:, 2489–2493. [CrossRef] [PubMed]
    [Google Scholar]
  3. Burrows J. M. , Burrows S. R. , Poulsen L. M. , Sculley T. B. , Moss D. J. , Khanna R. . ( 1996; ). Unusually high frequency of Epstein-Barr virus genetic variants in Papua New Guinea that can escape cytotoxic T-cell recognition: implications for virus evolution. . J Virol 70:, 2490–2496.[PubMed]
    [Google Scholar]
  4. Burrows J. M. , Bromham L. , Woolfit M. , Piganeau G. , Tellam J. , Connolly G. , Webb N. , Poulsen L. , Cooper L. et al. ( 2004; ). Selection pressure-driven evolution of the Epstein-Barr virus-encoded oncogene LMP1 in virus isolates from Southeast Asia. . J Virol 78:, 7131–7137. [CrossRef] [PubMed]
    [Google Scholar]
  5. Chang C. M. , Yu K. J. , Mbulaiteye S. M. , Hildesheim A. , Bhatia K. . ( 2009; ). The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: a need for reappraisal. . Virus Res 143:, 209–221. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chen Y. Y. , Chang K. L. , Chen W. G. , Shibata D. , Hayashi K. , Weiss L. M. . ( 1998; ). Epstein-Barr virus-associated nuclear antigen-1 carboxy-terminal gene sequences in Japanese and American patients with gastric carcinoma. . Lab Invest 78:, 877–882.[PubMed]
    [Google Scholar]
  7. Chu P. G. , Chang K. L. , Chen W. G. , Chen Y. Y. , Shibata D. , Hayashi K. , Bacchi C. , Bacchi M. , Weiss L. M. . ( 1999; ). Epstein-Barr virus (EBV) nuclear antigen (EBNA)-4 mutation in EBV-associated malignancies in three different populations. . Am J Pathol 155:, 941–947. [CrossRef] [PubMed]
    [Google Scholar]
  8. de Campos-Lima P. O. , Gavioli R. , Zhang Q. J. , Wallace L. E. , Dolcetti R. , Rowe M. , Rickinson A. B. , Masucci M. G. . ( 1993; ). HLA-A11 epitope loss isolates of Epstein-Barr virus from a highly A11+ population. . Science 260:, 98–100. [CrossRef] [PubMed]
    [Google Scholar]
  9. de Campos-Lima P. O. , Levitsky V. , Brooks J. , Lee S. P. , Hu L. F. , Rickinson A. B. , Masucci M. G. . ( 1994; ). T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues. . J Exp Med 179:, 1297–1305. [CrossRef] [PubMed]
    [Google Scholar]
  10. Edwards R. H. , Seillier-Moiseiwitsch F. , Raab-Traub N. . ( 1999; ). Signature amino acid changes in latent membrane protein 1 distinguish Epstein-Barr virus strains. . Virology 261:, 79–95. [CrossRef] [PubMed]
    [Google Scholar]
  11. Ehlers B. , Spiess K. , Leendertz F. , Peeters M. , Boesch C. , Gatherer D. , McGeoch D. J. . ( 2010; ). Lymphocryptovirus phylogeny and the origins of Epstein–Barr virus. . J Gen Virol 91:, 630–642. [CrossRef] [PubMed]
    [Google Scholar]
  12. Furutsuki T. , Hosoya N. , Kawana-Tachikawa A. , Tomizawa M. , Odawara T. , Goto M. , Kitamura Y. , Nakamura T. , Kelleher A. D. et al. ( 2004; ). Frequent transmission of cytotoxic-T-lymphocyte escape mutants of human immunodeficiency virus type 1 in the highly HLA-A24-positive Japanese population. . J Virol 78:, 8437–8445. [CrossRef] [PubMed]
    [Google Scholar]
  13. Gavioli R. , Kurilla M. G. , de Campos-Lima P. O. , Wallace L. E. , Dolcetti R. , Murray R. J. , Rickinson A. B. , Masucci M. G. . ( 1993; ). Multiple HLA A11-restricted cytotoxic T-lymphocyte epitopes of different immunogenicities in the Epstein-Barr virus-encoded nuclear antigen 4. . J Virol 67:, 1572–1578.[PubMed]
    [Google Scholar]
  14. Görzer I. , Niesters H. G. , Cornelissen J. J. , Puchhammer-Stöckl E. . ( 2006; ). Characterization of Epstein-Barr virus Type I variants based on linked polymorphism among EBNA3A, -3B, and -3C genes. . Virus Res 118:, 105–114. [CrossRef] [PubMed]
    [Google Scholar]
  15. Gratama J. W. , Oosterveer M. A. , Zwaan F. E. , Lepoutre J. , Klein G. , Ernberg I. . ( 1988; ). Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency. . Proc Natl Acad Sci U S A 85:, 8693–8696. [CrossRef] [PubMed]
    [Google Scholar]
  16. Habeshaw G. , Yao Q. Y. , Bell A. I. , Morton D. , Rickinson A. B. . ( 1999; ). Epstein-Barr virus nuclear antigen 1 sequences in endemic and sporadic Burkitt’s lymphoma reflect virus strains prevalent in different geographic areas. . J Virol 73:, 965–975.[PubMed]
    [Google Scholar]
  17. Hislop A. D. , Taylor G. S. , Sauce D. , Rickinson A. B. . ( 2007; ). Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. . Annu Rev Immunol 25:, 587–617. [CrossRef] [PubMed]
    [Google Scholar]
  18. Junying J. , Herrmann K. , Davies G. , Lissauer D. , Bell A. , Timms J. , Reynolds G. M. , Hubscher S. G. , Young L. S. et al. ( 2003; ). Absence of Epstein-Barr virus DNA in the tumor cells of European hepatocellular carcinoma. . Virology 306:, 236–243. [CrossRef] [PubMed]
    [Google Scholar]
  19. Kanno H. , Nakatsuka S. , Iuchi K. , Aozasa K. . ( 2000; ). Sequences of cytotoxic T-lymphocyte epitopes in the Epstein-Barr virus (EBV) nuclear antigen-3B gene in a Japanese population with or without EBV-positive lymphoid malignancies. . Int J Cancer 88:, 626–632. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kashiwagi Y. , Kawashima H. , Sato S. , Ioi H. , Amaha M. , Takekuma K. , Hoshika A. , Oshiro H. , Matsubayashi J. , Mukai K. . ( 2007; ). Virological and immunological characteristics of fatal virus-associated haemophagocytic syndrome (VAHS). . Microbiol Immunol 51:, 53–62.[PubMed] [CrossRef]
    [Google Scholar]
  21. Kawa K. . ( 2003; ). Diagnosis and treatment of Epstein-Barr virus-associated natural killer cell lymphoproliferative disease. . Int J Hematol 78:, 24–31. [CrossRef] [PubMed]
    [Google Scholar]
  22. Kawa K. , Sawada A. , Koyama M. , Inoue M. . ( 2007; ). Epstein-Barr virus infection after unrelated cord blood transplantation: reactivation or reinfection?. Int J Hematol 85:, 267–269. [CrossRef] [PubMed]
    [Google Scholar]
  23. Khanna R. , Slade R. W. , Poulsen L. M. , Moss D. J. , Burrows S. R. , Nicholls J. , Burrows J. M. . ( 1997; ). Evolutionary dynamics of genetic variation in Epstein-Barr virus isolates of diverse geographical origins: evidence for immune pressure-independent genetic drift. . J Virol 71:, 8340–8346.[PubMed]
    [Google Scholar]
  24. Kikuta H. , Taguchi Y. , Tomizawa K. , Kojima K. , Kawamura N. , Ishizaka A. , Sakiyama Y. , Matsumoto S. , Imai S. et al. ( 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] [PubMed]
    [Google Scholar]
  25. Kimura H. . ( 2006; ). Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency?. Rev Med Virol 16:, 251–261. [CrossRef] [PubMed]
    [Google Scholar]
  26. McGeoch D. J. , Gatherer D. . ( 2007; ). Lineage structures in the genome sequences of three Epstein-Barr virus strains. . Virology 359:, 1–5. [CrossRef] [PubMed]
    [Google Scholar]
  27. Midgley R. S. , Blake N. W. , Yao Q. Y. , Croom-Carter D. S. G. , Cheung S. T. , Leung S. F. , Chan A. T. C. , Johnson P. J. , Huang D. et al. ( 2000; ). Novel intertypic recombinants of Epstein-Barr virus in the Chinese population. . J Virol 74:, 1544–1548. [CrossRef] [PubMed]
    [Google Scholar]
  28. Midgley R. S. , Bell A. I. , McGeoch D. J. , Rickinson A. B. . ( 2003; a). Latent gene sequencing reveals familial relationships among Chinese Epstein-Barr virus strains and evidence for positive selection of A11 epitope changes. . J Virol 77:, 11517–11530. [CrossRef] [PubMed]
    [Google Scholar]
  29. Midgley R. S. , Bell A. I. , Yao Q. Y. , Croom-Carter D. , Hislop A. D. , Whitney B. M. , Chan A. T. , Johnson P. J. , Rickinson A. B. . ( 2003; b). HLA-A11-restricted epitope polymorphism among Epstein-Barr virus strains in the highly HLA-A11-positive Chinese population: incidence and immunogenicity of variant epitope sequences. . J Virol 77:, 11507–11516. [CrossRef] [PubMed]
    [Google Scholar]
  30. Miller W. E. , Edwards R. H. , Walling D. M. , Raab-Traub N. . ( 1994; ). Sequence variation in the Epstein–Barr virus latent membrane protein 1. . J Gen Virol 75:, 2729–2740. [CrossRef] [PubMed]
    [Google Scholar]
  31. Ohshima K. , Kimura H. , Yoshino T. , Kim C. W. , Ko Y. H. , Lee S. S. , Peh S. C. , Chan J. K. . CAEBV Study Group ( 2008; ). Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD. . Pathol Int 58:, 209–217. [CrossRef] [PubMed]
    [Google Scholar]
  32. Oshima M. , Azuma H. , Okuno A. . ( 1999; ). High prevalence of Epstein-Barr virus type A strain with the 30 b.p. deletion of the latent membrane protein-1 gene in a Japanese population. . Pediatr Int 41:, 490–495. [CrossRef] [PubMed]
    [Google Scholar]
  33. Rickinson A. B. , Kieff E. . ( 2007; ). Epstein-Barr virus. . In Fields Virology, , 5th edn., pp. 2655–2700. Edited by Knipe D. M. , Howley P. M. . . Philadelphia:: Lippincott, Williams & Wilkins;.
    [Google Scholar]
  34. Sample J. , Young L. , Martin B. , Chatman T. , Kieff E. , Rickinson A. , Kieff E. . ( 1990; ). Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. . J Virol 64:, 4084–4092.[PubMed]
    [Google Scholar]
  35. Sandvej K. , Zhou X. G. , Hamilton-Dutoit S. . ( 2000; ). EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction. . J Pathol 191:, 127–131. [CrossRef] [PubMed]
    [Google Scholar]
  36. Schuster V. , Ott G. , Seidenspinner S. , Kreth H. W. . ( 1996; ). Common Epstein-Barr virus (EBV) type-1 variant strains in both malignant and benign EBV-associated disorders. . Blood 87:, 1579–1585.[PubMed]
    [Google Scholar]
  37. Sitki-Green D. , Edwards R. H. , Webster-Cyriaque J. , Raab-Traub N. . ( 2002; ). Identification of Epstein-Barr virus strain variants in hairy leukoplakia and peripheral blood by use of a heteroduplex tracking assay. . J Virol 76:, 9645–9656. [CrossRef] [PubMed]
    [Google Scholar]
  38. Sitki-Green D. , Covington M. , Raab-Traub N. . ( 2003; ). Compartmentalization and transmission of multiple Epstein-Barr virus strains in asymptomatic carriers. . J Virol 77:, 1840–1847. [CrossRef] [PubMed]
    [Google Scholar]
  39. Tierney R. J. , Edwards R. H. , Sitki-Green D. , Croom-Carter D. , Roy S. , Yao Q. Y. , Raab-Traub N. , Rickinson A. B. . ( 2006; ). Multiple Epstein-Barr virus strains in patients with infectious mononucleosis: comparison of ex vivo samples with in vitro isolates by use of heteroduplex tracking assays. . J Infect Dis 193:, 287–297. [CrossRef] [PubMed]
    [Google Scholar]
  40. Wang F. , Rivailler P. , Rao P. , Cho Y. . ( 2001; ). Simian homologues of Epstein-Barr virus. . Philos Trans R Soc Lond B Biol Sci 356:, 489–497. [CrossRef] [PubMed]
    [Google Scholar]
  41. Woodberry T. , Suscovich T. J. , Henry L. M. , Davis J. K. , Frahm N. , Walker B. D. , Scadden D. T. , Wang F. , Brander C. . ( 2005; ). Differential targeting and shifts in the immunodominance of Epstein–Barr virus-specific CD8 and CD4 T cell responses during acute and persistent infection. . J Infect Dis 192:, 1513–1524. [CrossRef] [PubMed]
    [Google Scholar]
  42. Xu Z. G. , Iwatsuki K. , Ohtsuka M. , Oyama N. , Matsui T. , Kaneko F. . ( 2000; ). Polymorphism analysis of Epstein-Barr virus isolates from patients with cutaneous natural killer/T-cell lymphoproliferative disorders: a possible relation to the endemic occurrence of these diseases in Japan. . J Med Virol 62:, 239–246. [CrossRef] [PubMed]
    [Google Scholar]
  43. Yao Q. Y. , Tierney R. J. , Croom-Carter D. , Cooper G. M. , Ellis C. J. , Rowe M. , Rickinson A. B. . ( 1996; ). Isolation of intertypic recombinants of Epstein-Barr virus from T-cell-immunocompromised individuals. . J Virol 70:, 4895–4903.[PubMed]
    [Google Scholar]
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