1887

Abstract

The HI-Z-encoded Epstein—Barr virus (EBV) replication activator (ZEBRA) is a key mediator of the switch from latency to productive cycle in EBV virus. Antibodies against ZEBRA are a marker of EBV reactivation and are regularly found among patients with infectious mononucleosis (IM) or nasopharyngeal carcinoma (NPC), but are only rarely found among healthy EBV-seropositive donors. In order to define the serologically reactive epitopes in the ZEBRA protein, we synthesized a set of overlapping peptides and tested them for reactivity with serum samples from EBV-seronegative persons, patients with NPC, IM, chronic fatigue syndrome, lymphoma or from healthy donors. Three major EBV-specific epitopes were found. These epitopes were further defined and optimized using substitution or truncation analogues of the peptides. Reactivity with epitope number 22 was found in 63% of NPC patients’ sera, with < 2% of healthy donors’ sera being positive. Serological reactivity with epitope number 19 was associated with IM (57% positive, 5% healthy donors positive). Serum antibodies against epitope 1 were found among healthy donors, but were significantly elevated among patients with NPC, IM or lymphomas. In conclusion, different serologically reactive epitopes in the ZEBRA protein associate with different EBV-associated diseases.

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1995-06-01
2024-04-20
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References

  1. Birx D. L., Redfield R. R., Tosato G. 1986; Defective regulation of Epstein–Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders. New England Journal of Medicine 314:874–879
    [Google Scholar]
  2. Chen J. Y., Chen C. J., Liu M. Y., Cho S. M., Hsu M. M., Lynn T. C., Lee H. H., Kuo S. L., Lai M. Y., Hsieh C. Y., Hu C. P., Yang C. S. 1987; Antibodies to Epstein–Barr virus specific DNase in patients with nasopharyngeal carcinoma and control groups. Journal of Medical Virology 23:11–21
    [Google Scholar]
  3. Cheng H. M., Foong Y. T., Sam C. K., Prasad U., Dillner J. 1991; Epstein–Barr virus nuclear antigen 1 linear epitopes that are reactive with IgA or IgG in sera from nasopharyngeal carcinoma patients or from healthy donors. Journal of Clinical Microbiology 29:2180–2186
    [Google Scholar]
  4. Cheng H. M., Foong Y. T., Mathew A., Sam C. K., Dillner J., Prasad U. 1993; Screening for nasopharyngeal carcinoma with an ELISA using the Epstein–Barr virus nuclear antigen EBNA-1: a complementary test to the IgA/VCA immunofluorescence assay. Journal of Virological Methods 42:45–52
    [Google Scholar]
  5. Countryman J., Miller G. 1985; Activation of expression of latent Epstein–Barr herpesvirus after gene transfer with a small subfragment of heterogeneous viral DNA. Proceedings of the National Academy of Sciences, USA 82:4085–4089
    [Google Scholar]
  6. Countryman J., Jenson H., Seibl R., Wolf H., Miller G. 1987; Polymorphic proteins encoded within the BZLF1 of defective and standard Epstein–Barr viruses disrupt latency. Virology 61:3672–3679
    [Google Scholar]
  7. de Thé G., Geser A., Day N. E., Tukei P. M., Williams E. H., Beri D. P., Smith P. G., Dean A. G., Bornkamm G. W., Feorino P., Henle W. 1978; Epidemiological evidence for causal relationship between Epstein–Barr virus and Burkitt′s lymphoma from a Ugandan prospective study. Nature 274:756–761
    [Google Scholar]
  8. Dillner J. 1991; Epstein–Barr virus. In Encyclopedia of Human Biology vol 3 pp 463–472 Edited by Dulbecco R. New York: Academic Press;
    [Google Scholar]
  9. Dillner J., Dillner L., Utter G., Eklund C., Rotola A., Costa S., Diluca D. 1990; Mapping of linear epitopes of human papillomavirus type 16: the L1 and L2 open reading frames. International Journal of Cancer 45:529–535
    [Google Scholar]
  10. Foong Y. T., Cheng M. M., Sam C. K., Dillner J., Hinderer W., Prasad U. 1990; Serum and salivary IgA antibodies against a defined epitope of the Epstein–Barr virus nuclear antigen (EBNA) are elevated in nasopharyngeal carcinoma. International Journal of Cancer 45:1061–1064
    [Google Scholar]
  11. Ginsburg M. 1990; Antibodies against the large subunit of the EBV-encoded ribonucleotide reductase in patients with nasopharyngeal carcinoma. International Journal of Cancer 45:1048–1053
    [Google Scholar]
  12. Henle W., Henle G. 1979; Seroepidemiology of the virus. In The Epstein–Barr Virus pp 61–78 Edited by Epstein M. A., Achong R. Berlin: Springer;
    [Google Scholar]
  13. Holmes G. P., Kaplan J. E., Gantz N. E., Komaroff A. L., Schonberger L. B., Strauss S. E., Jones J. F., Dubois R. E., Cunningham-Rundles C., Pahwa S., Tosato G., Zegans L. S., Purtilo D. T., Brown N., Schooley R. T., Brus I. 1988; Chronic Fatigue Syndrome: A working case definition. Annals of Internal Medicine 108:387–389
    [Google Scholar]
  14. Houghten R. A. 1985; General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proceedings of the National Academy of Sciences, USA 82:5131–5153
    [Google Scholar]
  15. Joab I., Nicolas J. C., Schwabb G., de Thé G., Clausse B., Perricaudet M., Zeng Y. 1991a; Detection of anti-Epstein– Barr virus transactivator (ZEBRA) antibodies in sera from patients with nasopharyngeal carcinoma. International Journal of Cancer 48:647–649
    [Google Scholar]
  16. Joab I., Triki H., Desaint Martin J., Perricaudet M., Nicolas J. C. 1991b; Detection of anti-Epstein–Barr virus transactivator (ZEBRA) antibodies in sera from patients with human immunodeficiency virus. Journal of Infectious Diseases 163:53–56
    [Google Scholar]
  17. Lehtinbn T., Lumio J., Dillner J., Hakama M., Knekt P., Lehtinen M., Teppo L., Leinikki P. 1993; Increased risk of malignant lymphoma indicated by elevated Epstein–Barr virus antibodies – a prospective study. Cancer Causes and Control 4:187–196
    [Google Scholar]
  18. Littler E., Newman W., Arrand J. R. 1990; Immunological response of nasopharyngeal carcinoma patients to the Epstein–Barr virus encoded thymidine kinase expressed in Escherichia coli . International Journal of Cancer 45:1028–1032
    [Google Scholar]
  19. Liu M. Y., Chou W. M., Nutter L., Hsu M. M., Chen J. Y. 1989; Antibody against Epstein–Barr virus DNA polymerase activity in sera of patients with nasopharyngeal carcinoma. Journal of Medical Virology 28:101–105
    [Google Scholar]
  20. Marklund G., Henle W., Henle G., Ernberg I. 1986; IgA antibodies in infectious mononucleosis. Scandinavian Journal of Infectious Disease 18:111–119
    [Google Scholar]
  21. Masucci G., Mellstedt H., Masucci M. G., Szigeti R., Ernberg I., Bjorkholm M., Tsukada K., Henle G., Henle W., Pearson G., Holm G., Biberfeld P., Johansson B., Klein G. 1984; Immunological characterization of Hodgkin′s and non-Hodgkin′s lymphoma patients with high antibody titers against EBV-associated antigens. Cancer Research 44:1288–1300
    [Google Scholar]
  22. Mathew A., Cheng M. M., Sam C. K., Joab I., Prasad U., Cochet C. 1994; A high incidence of serum IgG antibodies to the Epstein–Barr virus replication activator protein in nasopharyngeal carcinoma. Cancer Immunology Immunotherapy 38:68–70
    [Google Scholar]
  23. Mueller N., Evans A., Harris N. L., Comstock G. W., Jellum E., Magnus K., Orentreich N., Polk B. F., Vogelman J. 1989; Hodgkin′s disease and Epstein–Barr virus: altered antibody pattern before diagnosis. New England Journal of Medicine 320:689–695
    [Google Scholar]
  24. Mueller N., Mohar A., Evans A., Harris N. L. 1991; Epstein–Barr virus antibody patterns preceding the diagnosis of non-Hodgkin′s lymphoma. International Journal of Cancer 49:387–393
    [Google Scholar]
  25. Schooley R. T., Carey R. W., Miller G., Henle W., Eastman R., Mark E. J., Kenyon K., Wheeler E. O., Rubin R. H. 1986; Acyclovir treatment in chronic mononucleosis. Annals of Internal Medicine 104:636–643
    [Google Scholar]
  26. Zeng Y., Zhong J. M., Li H. Y., Wang P. S., Tang H., Ma Y. R., Zhu J. S., Pan W. J., Liu Y. X., Wei Z. N., Chen J. Y., Mo Y. K., Li E. J., Tan B. F. 1983; Follow-up studies on Epstein–Barr virus IgA VCA antibody-positive persons in Zangwu county, China. Intervirology 20:190–194
    [Google Scholar]
  27. Zeng Y., Zhang L. G., Li H. Y., Jan M. G., Zhang Q., Wu Y. C., Wang Y. S., Su G. R. 1985; Serological mass survey for early detection of nasopharyngeal carcinoma in Wuzhou City, China. International Journal of Cancer 29:139–141
    [Google Scholar]
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