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Expression of Virus-Associated Functions in Cells Transformed in Vitro by Epstein-Barr Virus: Epstein-Barr Virus Cell Surface Antigen and Virus-Release from Transformed Cells

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Immune Deficiency and Cancer

Abstract

Epstein-Barr virus (EBV) infects resting human B lymphocytes in vitro and induces up to 10% of the infected cells to proliferate as measured in a clonal transformation assay (1–5). This virus also infects B lymphocytes in vivo; up to 20% of the peripheral B cells in patients with infectious mononucleosis (IM) express an EBV-associated nuclear antigen, EBNA (6), When peripheral lymphocytes from IM patients are collected and cloned directly in soft agar, some B cells are found to proliferate indefinitely and to express EBNA (7). Although it is not known that virus infections in vitro and in vivo are functionally equivalent, no differences between B cells infected in vitro and in vivo have yet been identified once the cells are studied in vitro. We have studied cells transformed by EBV in vitro with the hope that such studies will help to define characteristics of some of the cells infected by EBV in vivo. The advantage of studying cells transformed in vitro is that we can chart their history from their exposure to EBV to the time of study.

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References

  1. Pope, J.H., Home, M.K., and Scott, W. Transformation of foetal human leukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int. J. Cancer, 3:857, 1968.

    Article  PubMed  CAS  Google Scholar 

  2. Pattengale, P.K., Smith, R.W., and Gerber, P. Selective transformation of B lymphocytes by EB virus. Lancet, ii:93, 1973.

    Article  Google Scholar 

  3. Yamamoto, N. and Hinuma, Y. Clonal transformation of human leukocytes by Epstein-Barr virus in soft agar. Int. J. Cancer, 17:191, 1976.

    Article  PubMed  CAS  Google Scholar 

  4. Sugden, B. and Mark, W. Clonal transformation of adult human leukocytes by Epstein-Barr virus. J. Virol., 23:503, 1977.

    PubMed  CAS  Google Scholar 

  5. Henderson, E., Miller, G., Robinson, J., and Heston, L. Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology, 76:152, 1977.

    Article  PubMed  CAS  Google Scholar 

  6. Robinson, J.E., Smith, D., and Niederraan, J. Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis. J. Exp. Med., 153:235, 1981.

    Article  PubMed  CAS  Google Scholar 

  7. Hinuma, Y. and Katsuki, T. Colonies of EBNA-positive cells in soft agar from peripheral leukocytes of infectious mononucleosis patients. Int. J. Cancer, 21:426, 1978.

    Article  PubMed  CAS  Google Scholar 

  8. Reedman, B.M. and 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, 11:499, 1973.

    Article  PubMed  CAS  Google Scholar 

  9. van Santen, V., Cheung, A., and Kieff, E. Epstein-Barr virus RNA. VII. Size and direction of transcription of virus-specific cytoplasmic RNAs in a transformed cell line. Proc. Natl. Acad. Sci. USA, 78:1930, 1981.

    Article  PubMed  Google Scholar 

  10. Kintner, C. and Sugden, B. Conservation and progressive methylation of Epstein-Barr virus DNA sequences in transformed cells. J. Virol., 38:305, 1981.

    PubMed  CAS  Google Scholar 

  11. Lerner, M.R., Andrews, N.C., Miller, G., and Steitz, J.A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA, 78: 805, 1981.

    Article  PubMed  CAS  Google Scholar 

  12. Svedmyr, E. and Jondal, M. Cytotoxic effector cells specific for B cell lines transformed by Epstein-Barr virus are present in patients with infectious mononucleosis. Proc. Natl. Acad. Sci. USA, 72:1622, 1975.

    Article  PubMed  CAS  Google Scholar 

  13. Royston, I., Sullivan, J.L., Periman, P.O., and Perlin, E. Cell-mediated immunity to Epstein-Barr-virus-transformed lymphoblastoid cells in acute infectious mononucleosis. N. Engl. J. Med., 293:1159, 1975.

    Article  PubMed  CAS  Google Scholar 

  14. Svedmyr, E., Jondal, M., Henle, W., Weiland, O., Rorabo, L., and Klein, G. EBV-specific killer T cells and serologic responses after onset of infectious mononucleosis. J. Clin. Lab. Immunol., 1:225, 1978.

    PubMed  CAS  Google Scholar 

  15. Sugamura, K. and Hinuma, Y. In vitro induction of cytotoxic T lymphocytes specific for Epstein-Barr virus-transformed cells: kinetics of autologous restimulation. J. Immunol., 124:1045, 1980.

    PubMed  CAS  Google Scholar 

  16. Tanaka, Y., Sugamura, K., Hinuma, Y., Sato, H., and Okochi, K. Memory of Epstein-Barr virus-specific cytotoxic T cells in normal seropositive adults as revealed by an in vitro restimulation method. J. Immunol., 125:1426, 1980.”

    PubMed  CAS  Google Scholar 

  17. Misko, I.S., Moss, D.J., and Pope, J.H. HLA antigen-related restriction of T lymphocyte cytotoxicity to Epstein-Barr virus. Proc. Natl. Acad. Sci. USA, 77:4247, 1980.

    Article  PubMed  CAS  Google Scholar 

  18. Tsoukas, C.D., Fox, R.I., Slovin, S.F., Carson, D.A., Pellegrino, M., Fong, S., Pasquali, J.-L., Ferrone, S., Kung, P., and Vaughan, J.H. T lymphocyte-mediated cytotoxicity against autologous EBV-genome-bearing B cells. J. Immunol., 126:1742, 1981.

    PubMed  CAS  Google Scholar 

  19. Rickinson, A.B., Moss, D.J., Allen, D.J., Wallace, L.E., Rowe, M., and Epstein, M.A. Reactivation of Epstein-Barr virus-specific cytotoxic T cells by in vitro stimulation with autologous lymphoblastoid cell line. Int. J. Cancer, 27:593, 1981.

    Article  PubMed  CAS  Google Scholar 

  20. Lipinski, M., Fridman, W.H., Tursz, T., Vincent, C., Pious, D., and Fellous, M. Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. J. Exp. Med., 150:1310, 1979.

    Article  PubMed  CAS  Google Scholar 

  21. Kintner, C. and Sugden, B. Identification of determinants unique to the surfaces of cells transformed by Epstein-Barr virus. Nature, 294:458, 1981.

    Article  PubMed  CAS  Google Scholar 

  22. Slovin, S.F., Frisman, D.M., Tsoukas, C.D., Royston, I., Baird, S.M., Wormsley, S.B., Carson, D.A., and Vaughan, J.H. Membrane antigen on Epstein-Barr virus-infected human B cells recognized by a monoclonal antibody. Proc. Natl. Acad. Sci. USA, 79:2649, 1982.

    Article  PubMed  CAS  Google Scholar 

  23. Rowe, M., Hildreth, J.E.K., Rickinson, A.B., and Epstein, M.A. Monoclonal antibodies to Epstein-Barr virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T cell cytotoxicity. Int. J. Cancer, 29:373, 1982.

    Article  PubMed  CAS  Google Scholar 

  24. Thorley-Lawson, D.A., Edson, C.M., and Geilinger, K. Epstein-Barr virus antigens — a challenge to modern biochemistry. In: G. Klein and S. Weinhouse (eds.), Advances in Cancer Research. Vol. 36, pp. 295–348. New York: Academic Press, 1982.

    Google Scholar 

  25. Sugden, B., Phelps, M., and Domoradzki, J. Epstein-Barr virus DNA is amplified in transformed lymphocytes. J. Virol., 31: 590, 1979.

    PubMed  CAS  Google Scholar 

  26. Wilson, G. and Miller, G. Recovery of Epstein-Barr virus from nonproducer neonatal human lymphoid cell transformants. Virology, 95:351, 1979.

    Article  PubMed  CAS  Google Scholar 

  27. Thorley-Lawson, D.A., Schooley, R.T., Bhan, A.K., and Nadler, L.M. Epstein-Barr virus superinduces a new human B cell differentiation antigen (B-last-1) expressed on transformed cells. Cell, 30:415, 1982.

    Article  PubMed  CAS  Google Scholar 

  28. Fu, S.M. and Hurley, J.N. Human cell lines containing Epstein-Barr virus but distinct from the common B cell lymphoblastoid lines. Proc. Natl. Acad. Sci. USA, 76:6637, 1979.

    Article  PubMed  CAS  Google Scholar 

  29. Galfre, G. and Milstein, C. Preparation of monoclonal antibodies: strategies and procedures. In: J.J. Langone and H. van Vunakis (eds.), Method in Enzymology. Vol. 73, pp. 3–46. New York: Academic Press, 1981.

    Google Scholar 

  30. Sugden, B. and Metzenberg, S. Characterization of an antigen whose cell surface expression is induced by infection with Epstein-Barr virus. J. Virol., 46:800, 1983.

    PubMed  CAS  Google Scholar 

  31. Parham, P., Barnstable, C.J., and Bodmer, W.F. Use of monoclonal antibody (W6/32) in structural studies of HLA-A,B,C antigens. J. Immunol., 123: 342, 1979.

    PubMed  CAS  Google Scholar 

  32. Strominger, J.L., Mann, D.L., Parham, P., Robb, R., Springer, T., and Terhorst, C. Structure of HLA-A and B antigens isolated from cultured human lymphocytes. Cold Spring Harbor Symp. Quant. Biol., 41:323, 1977.

    Article  Google Scholar 

  33. Brodsky, F.M., Parham, P., Barnstable, C.J., Crumpton, M.J., and Bodmer, W.F. Monoclonal antibodies for analysis of the HLA system. Immunological Rev., 47:3, 1979.

    Article  CAS  Google Scholar 

  34. Olsnes, S., Fernandez-Puentes, C., Carrasco, L., and Vasques, D. Ribosome inactivation by the toxic lectins abrin and ricin. Kinetics of the enzymic activity of the toxic A-chains. Eur. J. Biochem., 60:281, 1975.

    Article  PubMed  CAS  Google Scholar 

  35. Cawley, D.B., Herschman, H.R., Gilliland, D.G., and Collier, R.J. Epidermal growth factor — toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. Cell, 22:563, 1980.

    Article  PubMed  CAS  Google Scholar 

  36. Klein, G., Giovanella, B.C., Lindahl, T., Fialkow, P.J., Singh, S., and Stehlin, J.S. Direct evidence for the presence of Epstein-Barr virus DNA and nuclear antigen in malignant epithelial cells from patients with poorly differentiated carcinoma of nasopharynx. Proc. Natl. Acad. Sci. USA, 71:4737, 1974.

    Article  PubMed  CAS  Google Scholar 

  37. Calnek, B.W. and Hitchner, S.B. Localization of viral antigen in chickens infected with Marek’s disease herpesvirus. J. Natl. Cancer Inst., 43:935, 1969.

    PubMed  CAS  Google Scholar 

  38. Nazerran, K. and Witter, R.L. Cell-free transmission and in vivo replication of Marek’s disease virus. J. Virol., 5:388, 1970.

    Google Scholar 

  39. Andersson, U., Bird, A.G., Britton, S., and Palacios, R. Humoral and cellular immunity studied at the cell level from birth to two years of age. Immunological Rev., 57:5, 1981.

    Article  Google Scholar 

  40. Miller, G. and Lipman, M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc. Natl. Acad. Sci. USA, 70:190, 1973.

    Article  PubMed  CAS  Google Scholar 

  41. Mark, W.H. Transformation of adult human lymphocytes in vitro by Epstein-Barr virus. Doctoral thesis, University of Wisconsin, Madison, 1981.

    Google Scholar 

  42. Zinkernagel, R.M. and Rosenthal, K.L. Experiments and speculation on anti-viral specificity of T and B cells. Immunological Rev., 58:131, 1981.

    Article  CAS  Google Scholar 

  43. Henle, W. and Henle, G. Seroepidemiology of the virus. In; M.A. Epstein and B.G. Achong (eds.), The Epstein-Barr Virus, pp. 61–78. Berlin: Springer-Verlag, 1979.

    Chapter  Google Scholar 

  44. Purtilo, D.T., Sakamoto, K., Saemundsen, A.K., Sullivan, J.L., Synnerholm, A-C., Anvret, M., Pritchard, J., Sloper, C., Seiff, C., Pincott, J., Pachman, L., Rich, K., Cruzi, F., Cornet, J., Collins, R., Barnes, N., Knight, J., Sandstedt, B., and Klein, G. Documentation of Epstein-Barr virus in immunodeficient patients with life-threatening lymphoproliferative diseases by clinical, virological and immunopathological studies. Cancer Res., 41:4226, 1981.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. McArdle Laboratory, University of Wisconsin, Madison, WI, 53706, USA

    Bill Sugden

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  1. Bill Sugden
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  1. University of Nebraska Medical Center, Omaha, Nebraska, USA

    David T. Purtilo

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© 1984 Plenum Publishing Corporation

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Sugden, B. (1984). Expression of Virus-Associated Functions in Cells Transformed in Vitro by Epstein-Barr Virus: Epstein-Barr Virus Cell Surface Antigen and Virus-Release from Transformed Cells. In: Purtilo, D.T. (eds) Immune Deficiency and Cancer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4760-6_8

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  • DOI: https://doi.org/10.1007/978-1-4684-4760-6_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-4762-0

  • Online ISBN: 978-1-4684-4760-6

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