1887

Abstract

Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus homologous to the human T-lymphotropic virus type 1 (HTLV-1), induces a chronic expansion of the B lymphocyte population (persistent lymphocytosis) and the development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in cultures compared to that obtained with infected asymptomatic (42%) and control (57%) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among surviving B cells and the percentage of CA- producing B cells correlated with the extent of B cell survival, indicating that BLV replication in B lymphocytes may promote protection from cell death. B cell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be involved in some aspects of the B cell life-span. Finally, cell cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a slightly increased proportion of B cells in S phase compared to controls. Altogether, these data suggest that both BLV-induced B cell proliferation and extended survival are involved in the lymphocytotic stage encountered in BLV infection in sheep.

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1997-01-01
2022-05-28
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References

  1. Alexandersen S., Carpenter S., Christensen J., Storgaard T., Viuff B., Wannemuehler Y., Belousov J., Roth J. A. 1993; Identification of alternatively spliced mRNAs encoding potential new regulatory proteins in cattle infected with bovine leukemia virus. Journal of Virology 67:39–52
    [Google Scholar]
  2. Arnold L. W., Pennel C. A., McCray S. K., Clarke S. H. 1994; Development of B-1 cells: segregation of phosphatidyl choline-specific B cells to the B-1 population occurs after immunoglobulin gene expression. Journal of Experimental Medicine 179:1585–1595
    [Google Scholar]
  3. Birkebak T. A., Palmer G. H., Davis W. C., Knowles D. P., McElwain T. F. 1994; Association of GP51 expression and persistent CD5 + B-lymphocyte expansion with lymphomatogenesis in bovine leukemia virus infected sheep. Leukemia 8:1890–1899
    [Google Scholar]
  4. Cambier J. C., Ransom J. T. 1987; Molecular mechanisms of transmembrane signaling in B lymphocytes. Annual Review ofImmunology 5:175–199
    [Google Scholar]
  5. Cherney B. W., Bhatia K., Tosato G. 1994; A role for deregulated c-Myc expression in apoptosis of Epstein-Barr virus-immortalized B cells. Proceedings of the National Academy of Sciences, USA 91:12967–12971
    [Google Scholar]
  6. Chlichlia K., Moldenhauer G., Daniel P. T., Busslinger M., Gazzolo L., Schirrmacher V., Khazaie K. 1995; Immediate effects of reversible HTLV-1 tax function: T-cell activation and apoptosis. Oncogene 10:269–277
    [Google Scholar]
  7. Copeland K. F. T., Haaksma A. G. M., Goudsmidt J., Krammer P. H., Heeney J. L. 1994; Inhibition of apoptosis in T cells expressing human T cell leukemia virus type 1 tax. AIDS Research and Human Retroviruses 10:1259–1268
    [Google Scholar]
  8. Cornefert-Jensen F., Hare W. C. D., Stock N. D. 1969; Studies on bovine lymphosarcoma : formation of syncytia and detection of virus particles in mixed-cell cultures. International Journal of Cancer 4:507–519
    [Google Scholar]
  9. Cornil I., Delon P., Parodi A. L., Levy D. 1988; T-B cell cooperation for bovine leukemia virus expression in ovine lymphocytes. Leukemia 2:313–317
    [Google Scholar]
  10. Darzynkiewicz Z., Bruno S., Delbino G., Gorczyca W., Hotz M. A., Lassota P., Traganos F. 1992; Features of apoptotic cells measured by flow cytometry. Cytometry 13:795–808
    [Google Scholar]
  11. Derse D. 1988; Trans-acting regulation of bovine leukemia virus mRNA processing. Journal of Virology 62:1115–1119
    [Google Scholar]
  12. Diamond M. S., Alon R., Parkos C. A., Quinn M. T., Springer T. A. 1995; Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD18). Journal of Cell Biology 130:1473–1482
    [Google Scholar]
  13. Djilali S., Parodi A.-L., Levy D. 1987; Bovine leukemia virus replicates in sheep B lymphocytes under a T cell released factor. European Journal of Cancer and Clinical Oncology 23:81–85
    [Google Scholar]
  14. Dragone L. L., Barth R. K., Sitar K. L., Disbrow G. L., Frelinger J. G. 1995; Disregulat ion of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival. Proceedings of the National Academy of Sciences, USA 92:626–630
    [Google Scholar]
  15. Felber B. K., Derse D., Athanassopoulos M., Campbell M., Pavlakis G. N. 1989; Cross activation of the rex proteins of HTLV-1 and BLV and of the rev protein of HIV-1 and non reciprocal interactions with their RNA responsive elements. New Biologist 1:318–330
    [Google Scholar]
  16. Fujita M., Shiku H. 1995; Differences in sensitivity to induction of apoptosis among rat fibroblasts cells transformed by HTLV-1 tax gene or cellular nuclear oncogenes. Oncogene 11:15–20
    [Google Scholar]
  17. Gagliardini V., Fernandez P. A., Lee R. K. K., Drexler H. C. A., Rotello R. J., Fishman M. C., Yuan J. 1994; Prevention of vertebrate neuronal death by the rCrmA gene. Science 263:826–828
    [Google Scholar]
  18. Grassmann R., Dengler C., Muller-Fleckenstein I., Fleckenstein B., McGuire K., Dokhelar M.-C., Sodroski J. G., Haseltine W. A. 1989; Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type 1 X-region genes transduced by a Herpesvirus saimiri vector. Proceedings of the National Academy of Sciences, USA 86:3351–3355
    [Google Scholar]
  19. Groux H., Torpier G., Monte D., Mouton Y., Capron A., Ameisen J. C. 1992; Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. Journal of Experimental Medicine 175:331–340
    [Google Scholar]
  20. Haughton G., Arnold L. W., Whitmore A. C., Clarke S. H. 1993; B-1 cells are made, not born. Immunology Today 14:84–87
    [Google Scholar]
  21. Haury M., Freitas A., Hermitte V., Coutinho A., Hibner U. 1993; The physiology of bcl-2 expression in murine B lymphocytes. Oncogene 8:1257–1262
    [Google Scholar]
  22. Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. 1991; Induction of Bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115
    [Google Scholar]
  23. Henderson S., Huen D., Rowe M., Dawson C., Johnson G., Rickinson A. 1993; Epstein-Barr virus-encoded BHFR-1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proceedings of the National Academy of Sciences, USA 90:8479–8483
    [Google Scholar]
  24. Jeang Q. T., Boros I., Brady J., Radanovich M., Khoury G. 1988; Characterization of cellular factors that interact with the human T-cell leukemia virus type 1 p40X responsive 21 base pair sequence. Journal of Virology 62:4499–4509
    [Google Scholar]
  25. Katoh I., Yoshinaka Y., Ikawa Y. 1989; Bovine leukemia virus trans-activator p38tax activates heterologous promoters with a common sequence known as a cAMP-responsive element or the binding site of a cellular transcription factor ATF. EMBO Journal 8:497–503
    [Google Scholar]
  26. Katsumata M., Siegel R. M., Louie D. C., Miyashita T., Tsujimoto Y., Nowell P. C., Greene M. I., Reed J. C. 1992; Differential effects of Bcl-2 on T and B cells in transgenic mice. Proceedings of the National Academy of Sciences, USA 89:11376–11380
    [Google Scholar]
  27. Keech C. L., Brandon M. R. 1991; Workshop findings on the ovine homolog of CD5. Veterinary Immunology and Immunopathology 27:103–107
    [Google Scholar]
  28. Leno M., Simpson R. M., Bowers F. S., Kindt T. J. 1995; Human T lymphocyte virus 1 from a leukemogenic cell line mediates in vivo and in vitro lymphocyte apoptosis. Journal of Experimental Medicine 181:1575–1580
    [Google Scholar]
  29. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. 1989; Bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 57:79–88
    [Google Scholar]
  30. Mager A., Masengo R., Mammerickx M., Letesson J.-J. 1994; T cell proliferative response to bovine leukaemia virus (BLV): identification of T cell epitopes on the major core protein (p24) in BLV-infected cattle with normal haematological values. Journal of General Virology 75:2223–2231
    [Google Scholar]
  31. Mammerickx M., Palm R., Portetelle D., Burny A. 1988; Experimental transmission of leukosis in sheep : latency period of the tumoral disease. Leukemia 2:103–107
    [Google Scholar]
  32. Matheise J. P., Delcommenne M., Mager A., Didembourg C. H., Letesson J. J. 1992; CD5 + B cells from bovine leukemia virus infected cows are activated cycling cells responsive to interleukin 2. Leukemia 6:304–309
    [Google Scholar]
  33. Murakami K., Okada K., Ikawa Y., Aida Y. 1994; Bovine leukemia virus induces CD5 - B cell lymphoma in sheep despite temporarily increasing CD5 + B cells in asymptomatic stage. Virology 202:458–465
    [Google Scholar]
  34. Ohno K., Nakano T., Matsumoto Y., Watari T., Goitsuka R., Nakayma H., Tsujimoto H., Hasegawa A. 1993; Apoptosis induced by tumor necrosis factor in cells chronically infected with feline immunodeficiency virus. Journal of Virology 67:2429–2433
    [Google Scholar]
  35. Oscar Pintado C., Perez de la Lastra J., Llanes D. 1995; A monoclonal antibody to an ovine gp130 molecule inhibits homotypic aggregation induced by anti-CD43 monoclonal antibodies of ruminant leukocytes. Immunology Letters 45:81–85
    [Google Scholar]
  36. Pan H., Griep A. E. 1994; Altered cell cycle regulation in the lens of HPV-16 E6 and E7 transgenic mice: implication for tumor suppressor gene function in development. Genes and Development 8:1285–1299
    [Google Scholar]
  37. Persaud D., Munoz J. L., Tarsis S. L., Parks E. S., Parks W. P. 1995; Time course and cytokine dependence of human T-cell lymphotropic virus type 1-lymphocyte transformation as revealed by a microtiter infectivity assay. Journal of Virology 69:6297–6303
    [Google Scholar]
  38. Powers M. A., Radke K. 1992; Activation of bovine leukemia virus transcription in lymphocytes from infected sheep: rapid transition through early to late gene expression. Journal of Virology 66:4769–4777
    [Google Scholar]
  39. Rashtchian A. 1994; Amplification of RNA. PCR Methods and Applications 4: supplementum S83–S91
    [Google Scholar]
  40. Rojko J. L., Fulton R. M., Rezanka L. J., Williams L. L., Copelan E., Cheney C. M., Reichel G. S., Neil J. C., Mathes L. E., Fisher T. G., Cloyd M. W. 1992; Lymphocytotoxic strains of feline leukemia virus induce apoptosis in feline T4-thymic lymphoma cells. Laboratory Investigation 66:418–426
    [Google Scholar]
  41. Saha K., Yuen P. H., Wong P. K. Y. 1994; Murine retrovirus- induced depletion of T cells is mediated through activation-induced death by apoptosis. Journal of Virology 68:2735–2740
    [Google Scholar]
  42. SAS Institute 1990 SAS/STAT User’s Guide, 4th edn. Cory, N. C: SAS Institute;
    [Google Scholar]
  43. Schwartz I., Levy D. 1994; Pathobiology of bovine leukemia virus. Veterinary Research 25:521–536
    [Google Scholar]
  44. Schwartz I., Bensaid A., Polack B., Perrin B., Berthelemy M., Levy D. 1994; In vivo leukocyte tropism of bovine leukemia virus in sheep and cattle. Journal of Virology 68:4589–4596
    [Google Scholar]
  45. Symond H., Krall L., Saenz Robles M., Lowe S., Jacks T., Van Dyke T. 1994; p53-dependent apoptosis suppresses tumor growth and progression in vivo . Cell 78:703–711
    [Google Scholar]
  46. Umehara F., Nakamura A., Izumo S., Kubota R., Ijichi S., Kashio N., Hashimoto K., Usuku K., Sato E., Osame M. 1994; Apoptosis of T lymphocytes in the spinal cord lesions in HTLV-1-associated myelopathy: a possible mechanism to control viral infection in the central nervous system. Journal of Neuropathology and Experimental Neurology 53:617–624
    [Google Scholar]
  47. Van der Maaten M. J., Miller J. M., Boothe A. D. 1974; Replicating type-C virus particles in monolayer cell cultures of tissue from cattle with lymphosarcoma. Journal of the National Cancer Institute 52:491–497
    [Google Scholar]
  48. Vaux D. L., Cory S., Adams J. M. 1988; Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335:440–442
    [Google Scholar]
  49. Wells S. M., Kantor A. B., Stall A. M. 1994; CD43 (S7) expression identifies peripheral B cell subsets. Journal of Immunology 153:5503–5515
    [Google Scholar]
  50. Willems L., Heremans H., Chen G., Portetelle D., Billiau A., Burny A., Kettmann R. 1990; Cooperation between bovine leukaemia virus transactivator protein and Ha-ras oncogene product in cellular trans-formation. EMBO Journal 9:1577–1581
    [Google Scholar]
  51. Yamada T., Yamaoka S., Goto T., Nakai M., Tsujimoto Y., Hatanaka M. 1994; The human T-cell leukemia virus type 1 tax protein induces apoptosis which is blocked by the Bcl-2 protein. Journal of Virology 68:3374–3379
    [Google Scholar]
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