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Experimental Carcinogenicity by the Virus In Vivo

  • Chapter
The Epstein-Barr Virus

Abstract

Epstein-Barr virus (EBV) induces lymphoid neoplasms in marmosets and owl monkeys (Shope et al., 1973; Epstein et al., 1973 a, b, 1975). The tumors caused experimentally resemble Burkitt’s lymphomas (BL) in several ways: they arise in the germinal centers of lymphoid follicles, they contain many EBV DNA copies per cell, and they express the EBV nuclear antigen (EBNA). Not all individuals of susceptible species infected in the laboratory manifest malignant disease. Some seem to contract a benign lymphoproliferative syndrome while others remain healthy. Thus a spectrum of responses, such as is seen in human EBV infections, also occurs after infection of new-world primates in the laboratory.

The experiments described in this chapter which were carried out in the author’s laboratory could not have been possible without the collaboration of T. C. Shope, J. Robinson, E. Henderson, and W. A. Andiman. Levin Waters provided patient and conservative guidance in interpretation of the pathology. W. Webb and D. Coope were expert in care of marmosets and handling their tissues and cells. Work on experimental tumorigenicity by EBV was supported by grants VC-107 from the American Cancer Society and grants CA-12055 and CA-16038 from the National Cancer Institute. G. M. is an investigator of the Howard Hughes Medical Institute.

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References

  • Adams, A., Bjursell, G., Kaschka-Dierich, C., Lindahl, T.: Circular Epstein-Barr virus genomes of reduced size in a human lymphoid cell line of infectious mononucleosis origin. J. Virol. 22, 373–380 (1977)

    PubMed  CAS  Google Scholar 

  • Andiman, W. A., Miller, G.: Properties of Epstein-Barr virus transformed woolly monkey lymphocytes. Proc. Soc. Exp. Biol. Med. 157, 489–493 (1978)

    PubMed  CAS  Google Scholar 

  • Bar, R. S., Deler, C. J., Clausen, K. P., Hurtubise, P., Henle, W., Hewetson, J. F.: Fatal infectious mononucleosis in a family. N. Engl. J. Med. 290, 363–367 (1974)

    Article  PubMed  CAS  Google Scholar 

  • Blacklow, N. R., Watson, B. K., Miller, G., Jacobson, B. M.: Mononucleosis with heterophil antibodies and EB Virus infection. Acquisition by an elderly patient in hospital. Am. J. Med. 51, 549–552 (1971)

    Article  PubMed  CAS  Google Scholar 

  • Burkitt, D. P.: Etiology of Burkitt’s lymphoma — an alternative hypothesis to a vectored virus. J. Natl. Cancer Inst. 42, 19–28 (1969)

    PubMed  CAS  Google Scholar 

  • Deinhardt, F., Falk, L., Wolfe, L. G., Paciga, J., Johnson, D.: Response of marmosets to experimental infection with Epstein-Barr virus. In: Oncogenesis and herpesviruses II. de-Thé, G., Epstein, M. A., zur Hausen, H. (eds.), Part 2, pp. 161–168. Lyon: IARC 1975

    Google Scholar 

  • Diamondopoulos, G. Ph., McLane, M. F.: Effect of host age, virus dose, and route of inoculation on tumor incidence, latency, and morphology in Syrian hamsters inoculated intravenously with oncogenic DNA simian virus 40. J. Natl. Cancer Inst. 55, 479–482 (1975)

    Google Scholar 

  • Epstein, M. A., Hunt, R. D., Rabin, H.: Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus) I. Reticuloproliferative disease in an inoculated animal. Int. J. Cancer 12, 309–318 (1973a)

    Article  PubMed  CAS  Google Scholar 

  • Epstein, M. A., Rabin, H., Ball, G., Rickinson, A.B., Jarvis, J., Meléndez, L. V.: Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus) II. EB virus in a cell line from an animal with reticuloproliferative disease. Int. J. Cancer 12, 319–332 (1973b)

    Article  PubMed  CAS  Google Scholar 

  • Epstein, M. A., zur Hausen, H., Ball, G., Rabin, H.: Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus) III. Serological and biochemical findings in an animal with reticuloproliferative disease. Int. J. Cancer 15, 17–22 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Falk, L., Wolfe, L., Deinhardt, F., Paciga, J., Dombos, L., Klein, G., Henle, W., Henle, G. Epstein-Barr virus: transformation of nonhuman primate lymphocytes in vitro. Int. J. Cancer 13, 363–376 (1974)

    Article  PubMed  CAS  Google Scholar 

  • Fialkow, P. J., Klein, G., Gartler, S. M., Clifford, P.: Clonal origin for individual Burkitt tumors. Lancet 1970 I, 384–386

    Article  Google Scholar 

  • Frank, A., Andiman, W., Miller, G.: Epstein-Barr virus and non-human primates: natural and experimental infection. Adv. Cancer Res. 23, 171–210 (1976)

    Article  PubMed  CAS  Google Scholar 

  • Harvey, J. S. (Jr.), Felsburg, P. J., Heberling, R. L., Kniker, W. T., Kalter, S. S.: Immunological competence in non-human primates: differences observed in four species. Clin. Exp. Immunol. 16, 267–278 (1974)

    CAS  Google Scholar 

  • Henderson, E., Miller, G., Robinson, J., Heston, L.: Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology 76, 152–163 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Henderson, E., Robinson, J., Frank, A., Miller, G.: Epstein-Barr virus: transformation of lymphocytes separated by size or exposed to bromodeoxyuridine and light. Virology 82, 196–205 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Henle, G., Henle, W.: Immunofluorescence in cells derived from Burkitt’s lymphoma. J. Bacteriol. 91, 1248–1256 (1966)

    PubMed  CAS  Google Scholar 

  • Henle, W., Diehl, V., Kohn, G., zur Hausen, H., Henle, G.: Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science 157, 1064–1065 (1967)

    Article  PubMed  CAS  Google Scholar 

  • Henle, G., Henle, W., Zajac, B., Pearson, G., Waubke, R., Scriba, M.: Differential reactivity of human serums with early antigens induced by Epstein-Barr virus. Science 169, 188–190 (1970)

    Article  PubMed  CAS  Google Scholar 

  • Henle, G., Henle, W., Llein, G., Gunvén, P., Morrow R.H., Ziegler L.L.: Antibodies to early Enstein-Barr virus-induced antigens in Burkitt’s lymphoma. J. Natl. Cancer Inst. 46, 861–871 (1971)

    PubMed  CAS  Google Scholar 

  • Klein, G.: Studies on the Epstein-Barr virus genome and the EBV-determined nuclear antigen in human malignant disease. Cold Spring Harbor Symp. Quant. Biol. 39, 783–790 (1975)

    PubMed  Google Scholar 

  • Leibold, W., Huldt, G., Flanagan, T. D., Andersson, M., Dalens, M., Wright, D. H., Voller, A., Klein, G.: Tumorigenicity of Epstein-Barr virus (EBV)-transformed lymphoid line cells in autologous squirrel monkeys. Int. J. Cancer 17, 533–541 (1976)

    Article  PubMed  CAS  Google Scholar 

  • Lindahl, T., Adams, A., Bjursell, G., Bornkamm, G. W., Kaschka-Dierich, C., Jehn, W.: Covalently closed circular duplex DNA of Epstein-Barr virus in a human lymphoid cell line. J. Mol. Biol. 102, 511–530 (1976)

    Article  PubMed  CAS  Google Scholar 

  • Lipman, M., Andrews, L., Niederman, J., Miller, G.: Direct visualization of enveloped herpes-like virus from throat washing with leukocyte transforming activity. J. Infect. Dis. 132, 520–523 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Lukes, R. J., Collins, R. D.: New approaches to the classification of the lymphomata. Br. J. Cancer 31, [Suppl. 2] 1–27 (1975)

    Google Scholar 

  • Meléndez, L. V., Hunt, R. D., Daniel, M. D.: Herpesvirus saimiri II. Experimentally induced malignant lymphoma in primates. Lab. Anim. Care 19, 378–386 (1969)

    PubMed  Google Scholar 

  • Menezes, J., Leibold, W., Klein, G.: Biological differences between Epstein-Barr virus strains with regard to lymphocyte transforming ability, superinfection and antigen induction. Exp. Cell Res. 92, 478–484 (1975)

    Article  CAS  Google Scholar 

  • Miller, G., Shope, T., Lisco, H., Stitt, D., Lipman, M.: Epstein-Barr virus: transformation, cytopathic changes and viral antigens in squirrel monkey and marmoset leukocytes. Proc. Natl. Acad. Sci. USA 69, 383–387 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Miller, G., Lipman, M.: Comparison of the yield of infectious virus from clones of human and simian lymphoblastoid lines transformed by Epstein-Barr virus. J. Exp. Med. 138, 1398–1412 (1973)

    Article  PubMed  CAS  Google Scholar 

  • Miller, G., Robinson, J., Heston, L., Lipman, M.: Differences between laboratory strains of Epstein-Barr virus based on immortalization, abortive infection and interference. Proc. Natl. Acad. Sci. USA 71, 4006–4010 (1974)

    Article  PubMed  CAS  Google Scholar 

  • Miller, G., Coope, D., Niederman, J., Pagano, J.: Biologic properties and viral surface antigens of Burkitt lymphoma and mononucleosis derived strains of Epstein-Barr virus released from transformed marmoset cells. J. Virol. 18, 1071–1080 (1976)

    PubMed  CAS  Google Scholar 

  • Miller, G., Shope, T., Coope, D., Waters, L., Pagano, J., Bornkamm, G. W., Henle, W.: Lymphoma in cotton-top marmosets after inoculation with Epstein-Barr virus: tumor incidence, histologic spectrum, antibody responses, demonstration of viral DNA, and characterization of viruses. J. Exp. Med. 145, 948–967 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Nilsson, K., Giovanella, B. C., Stehlin, J. S., Klein, G.: Tumorigenicity of human hematopoietic cell lines in athymic nude mice. Int. J. Cancer 19, 337–344 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Nonoyama, M., Huang, C. H., Pagano, J. S., Klein, G., Singh, S.: DNA of Epstein-Barr virus detected in tissue of Burkitt’s lymphoma and nasopharyngeal carcinoma. Proc. Natl. Acad. Sci. USA 70, 3265–3268 (1973)

    Article  PubMed  CAS  Google Scholar 

  • Pritchett, R. F., Hayward, S. D., Kieff, E. D.: DNA of Epstein-Barr virus. I. Comparative studies of the DNA of Epstein-Barr virus from HR-1 and B95–8 cells: size, structure and relatedness. J. Virol. 15, 556–569 (1975)

    PubMed  CAS  Google Scholar 

  • Rabin, H., Neubauer, R. H., Hopkins, R. F., III, Levy, B. M.: Characterization of lymphoid cell lines established from multiple Epstein-Barr virus (EBV) induced lymphomas in a cotton-topped marmoset. Int. J. Cancer 20, 44–50 (1977)

    Article  PubMed  CAS  Google Scholar 

  • 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 11, 499–520 (1973)

    Article  PubMed  CAS  Google Scholar 

  • Robinson, J. E., Andiman, W. A., Henderson, E., Miller, G.: Host-determined differences in expression of surface marker characteristics on human and simian lymphoblastoid cell lines transformed by Epstein-Barr virus. Proc. Natl. Acad. Sci. USA 74, 749–753 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Shope, T. C., Miller, G.: Epstein-Barr virus: Heterophile responses in squirrel monkeys inoculated with virus-transformed autologous leukocytes. J. Exp. Med. 137, 140–147 (1973)

    Article  PubMed  CAS  Google Scholar 

  • Shope, T., Dechairo, D., Miller, G.: Malignant lymphoma in cottontop marmosets after inoculation with Epstein-Barr virus. Proc. Natl. Acad. Sci. USA 70, 2487–2491 (1973)

    Article  PubMed  CAS  Google Scholar 

  • Shope, T. C.: Prevention of Epstein-Barr virus (EBV)-induced infection in cotton-topped marmosets by human serum containing EBV neutralizing activity. In: Oncogenesis and herpes viruses II. de-Thé, G., Epstein, M. A., zur Hausen, H. (eds.), Part 2, pp. 153–159. Lyon: IARC 1975

    Google Scholar 

  • Sugden, B., Summers, W. C., Klein, G.: Nucleic acid renaturation and restriction endonuclease cleavage analyses show that the DNA’s of a transforming and a non-transforming strain of Epstein-Barr virus share approximately 90% of their nucleotide sequences. J. Virol. 18, 765–775 (1976)

    PubMed  CAS  Google Scholar 

  • Sugden, B., Mark, W.: Clonal transformation of adult human leukocytes by Epstein-Barr virus. J. Virol. 23, 503–508 (1977)

    PubMed  CAS  Google Scholar 

  • Sugden, B.: Comparison of Epstein-Barr viral DNA’s in Burkitt lymphoma biopsy cells and in cells clonally transformed in vitro. Proc. Natl. Acad. Sci. USA 74, 4651–4655 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Trumper, P. A., Epstein, M. A., Giovanella, B. C., Finerty, S.: Isolation of infectious EB virus from the epithelial tumour cells of nasopharyngeal carcinoma. Int. J. Cancer 20, 655–662 (1977)

    Article  PubMed  CAS  Google Scholar 

  • Werner, J., Henle, G., Pinto, C. A., Haff, R. F., Henle, W.: Establishment of continuous lymphoblast cultures from leukocytes of gibbons (Hylobates lar). Int. J. Cancer 10, 557–567 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Werner, J., Pinto, C. A., Haff, R. F., Henle, W., Henle, G.: Response of gibbons to inoculation of Epstein-Barr virus. J. Infect. Dis. 126, 678–681 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Werner, J., Wolf, H., Apodaca, J., zur Hausen, H.: Lymphoproliferative disease in a cotton-top marmoset after inoculation with infectious mononucleosis-derived Epstein-Barr virus. Int. J. Cancer 15, 1000–1008 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Wolf, H., Werner, J., zur Hausen, H.: EBV DNA in nonlymphoid cells of nasopharyngeal carcinomas and in a malignant lymphoma obtained after inoculation of EBV into cotton-top marmosets. Cold Spring Harbor Symp. Quant. Biol. 39, 791–796 (1977)

    Google Scholar 

  • zur Hausen, H., Schulte-Holthausen, H., Klein, G., Henle, G., Henle, W., Clifford, P., Santesson, L.: EBV-; DNA in biopsies of Burkitt tumors and anaplastic carcinomas of the nasopharynx. Nature 228, 1056–1058 (1970)

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, School of Medicine, Yale University, 333 Cedar Street, New Haven, CT, 06510, USA

    G. Miller

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  1. G. Miller
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Editors and Affiliations

  1. Department of Pathology, The Medical School, University of Bristol, University Walk, Bristol, BS8 1TD, England

    M. A. Epstein M.A., M.D., Ph.D., D.Sc., F.R.C. Path., F.R.S.  & B. G. Achong M.B., B.Ch., B.A.O., M.D.  & 

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© 1979 Springer-Verlag Berlin Heidelberg

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Miller, G. (1979). Experimental Carcinogenicity by the Virus In Vivo. In: Epstein, M.A., Achong, B.G. (eds) The Epstein-Barr Virus. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-67236-1_16

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  • DOI: https://doi.org/10.1007/978-3-642-67236-1_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-67238-5

  • Online ISBN: 978-3-642-67236-1

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