Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1984 Mar;43(3):920–924. doi: 10.1128/iai.43.3.920-924.1984

Prevention of Epstein-Barr virus-induced B-cell outgrowth by interferon alpha.

J G Garner, M S Hirsch, R T Schooley
PMCID: PMC264271  PMID: 6321354

Abstract

An in vitro system for determining the efficacy of interferon alpha (IFN-alpha) in preventing B-cell outgrowth due to Epstein-Barr virus (EBV) was developed. Unfractionated cord blood mononuclear cells, T-cell-depleted cord blood mononuclear cells, or adult T-cell-depleted mononuclear cells were exposed to IFN-alpha for 18 to 20 h followed by incubation with the B95-8 strain of EBV for 2 h. B-cell outgrowth was monitored by microscopic examination, [3H]thymidine incorporation, and Epstein-Barr nuclear antigen detection. Cell density and viral inoculum both affected the sensitivity of outgrowth to IFN-alpha. IFN-alpha was most effective when added at each feeding after infection as well as before infection with EBV. The mean of the lowest IFN-alpha concentration tested at which transformation failed to occur after infection with the B95-8 strain of EBV at a 50% transforming dose of 10(2.0) to 10(3.0)/ml was similar for unfractionated cord blood mononuclear cells, T-cell-depleted cord blood mononuclear cells, and adult T-cell-depleted mononuclear cells. The B95-8 strain and clinical EBV isolates required similar IFN-alpha concentrations to prevent outgrowth. In this system, IFN-alpha at pharmacologically achievable concentrations prevented EBV-induced B-cell outgrowth. These data indicate that IFN-alpha deserves further study as a potential therapeutic agent for EBV-induced syndromes.

Full text

PDF
920

Selected References

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

  1. Bloom B. R. Interferons and the immune system. Nature. 1980 Apr 17;284(5757):593–595. doi: 10.1038/284593a0. [DOI] [PubMed] [Google Scholar]
  2. Doetsch P. W., Suhadolnik R. J., Sawada Y., Mosca J. D., Flick M. B., Reichenbach N. L., Dang A. Q., Wu J. M., Charubala R., Pfleiderer W. Core (2'-5')oligoadenylate and the cordycepin analog: inhibitors of Epstein--Barr virus-induced transformation of human lymphocytes in the absence of interferon. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6699–6703. doi: 10.1073/pnas.78.11.6699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gutterman J. U., Fine S., Quesada J., Horning S. J., Levine J. F., Alexanian R., Bernhardt L., Kramer M., Spiegel H., Colburn W. Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. Ann Intern Med. 1982 May;96(5):549–556. doi: 10.7326/0003-4819-96-5-549. [DOI] [PubMed] [Google Scholar]
  4. Hanto D. W., Frizzera G., Gajl-Peczalska J., Purtilo D. T., Klein G., Simmons R. L., Najarian J. S. The Epstein-Barr virus (EBV) in the pathogenesis of posttransplant lymphoma. Transplant Proc. 1981 Mar;13(1 Pt 2):756–760. [PubMed] [Google Scholar]
  5. Henderson E., Miller G., Robinson J., Heston L. Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology. 1977 Jan;76(1):152–163. doi: 10.1016/0042-6822(77)90292-6. [DOI] [PubMed] [Google Scholar]
  6. Henle G., Henle W., Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A. 1968 Jan;59(1):94–101. doi: 10.1073/pnas.59.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holmes A. R., Rasmussen L., Merigan T. C. Factors affecting the interferon sensitivity of human cytomegalovirus. Intervirology. 1978;9(1):48–55. doi: 10.1159/000148920. [DOI] [PubMed] [Google Scholar]
  8. Lai P. K., Alpers M. P., MacKay-Scollay E. M. Epstein-Barr herpesvirus infection: inhibition by immunologically induced mediators with interferon-like properties. Int J Cancer. 1977 Jul 15;20(1):21–29. doi: 10.1002/ijc.2910200106. [DOI] [PubMed] [Google Scholar]
  9. Lipman M., Andrews L., Niederman J., Miller G. Direct visualization of enveloped Epstein-Barr Herpesvirus in throat washing with leukocyte-transforming activity. J Infect Dis. 1975 Nov;132(5):520–523. doi: 10.1093/infdis/132.5.520. [DOI] [PubMed] [Google Scholar]
  10. Lvovsky E., Levine P. H., Fuccillo D., Ablashi D. V., Bengali Z. H., Armstrong G. R., Levy H. B. Epstein-Barr virus and Herpesvirus saimiri: sensitivity to interferons and interferon inducers. J Natl Cancer Inst. 1981 Jun;66(6):1013–1019. doi: 10.1093/jnci/66.6.1013. [DOI] [PubMed] [Google Scholar]
  11. Menezes J., Patel P., Dussault H., Joncas J., Leibold W. Effect of interferon on lymphocyte transformation and nuclear antigen production by Epstein-Barr virus. Nature. 1976 Apr 1;260(5550):430–432. doi: 10.1038/260430a0. [DOI] [PubMed] [Google Scholar]
  12. Miller D. The etiology of nasopharyngeal cancer and its management. Otolaryngol Clin North Am. 1980;13(3):467–475. [PubMed] [Google Scholar]
  13. Minato N., Reid L., Cantor H., Lengyel P., Bloom B. R. Mode of regulation of natural killer cell activity by interferon. J Exp Med. 1980 Jul 1;152(1):124–137. doi: 10.1084/jem.152.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morgan D. G., Niederman J. C., Miller G., Smith H. W., Dowaliby J. M. Site of Epstein-Barr virus replication in the oropharynx. Lancet. 1979 Dec 1;2(8153):1154–1157. doi: 10.1016/s0140-6736(79)92384-5. [DOI] [PubMed] [Google Scholar]
  15. Postic B., Dowling J. N. Susceptibility of clinical isolates of cytomegalovirus to human interferon. Antimicrob Agents Chemother. 1977 Apr;11(4):656–660. doi: 10.1128/aac.11.4.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reedman B. M., Klein G. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer. 1973 May;11(3):499–520. doi: 10.1002/ijc.2910110302. [DOI] [PubMed] [Google Scholar]
  17. Schubach W. H., Hackman R., Neiman P. E., Miller G., Thomas E. D. A monoclonal immunoblastic sarcoma in donor cells bearing Epstein-Barr virus genomes following allogeneic marrow grafting for acute lymphoblastic leukemia. Blood. 1982 Jul;60(1):180–187. [PubMed] [Google Scholar]
  18. Stitz L., Schellekens H. Influence of input multiplicity of infection on the antiviral activity of interferon. J Gen Virol. 1980 Jan;46(1):205–210. doi: 10.1099/0022-1317-46-1-205. [DOI] [PubMed] [Google Scholar]
  19. Thorley-Lawson D. A., Chess L., Strominger J. L. Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes. J Exp Med. 1977 Aug 1;146(2):495–508. doi: 10.1084/jem.146.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Thorley-Lawson D. A. The suppression of Epstein-Barr virus infection in vitro occurs after infection but before transformation of the cell. J Immunol. 1980 Feb;124(2):745–751. [PubMed] [Google Scholar]
  21. Thorley-Lawson D. A. The transformation of adult but not newborn human lymphocytes by Epstein Barr virus and phytohemagglutinin is inhibited by interferon: the early suppression by T cells of Epstein Barr infection is mediated by interferon. J Immunol. 1981 Mar;126(3):829–833. [PubMed] [Google Scholar]
  22. Ziegler J. L. Burkitt's lymphoma. N Engl J Med. 1981 Sep 24;305(13):735–745. doi: 10.1056/NEJM198109243051305. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES