1887

Abstract

Bovine leukaemia virus (BLV) is in the family of oncogenic retroviruses which includes human T cell leukaemia virus (HTLV). BLV infects B lymphocytes and induces a non-neoplastic persistent lymphocytosis (PL) of B lymphocytes in cattle. A characteristic of BLV- and HTLV-induced disease is spontaneous lymphocyte proliferation of cultured peripheral blood mononuclear cells (PBMC). To investigate the role of virus expression on lymphocyte survival and proliferation, we evaluated cell cycle position, apoptosis and virus expression on a single-cell basis of cultured PBMC from BLV-infected PL cattle, BLV-infected non-PL cattle and uninfected cattle. Results demonstrated that the majority of bovine B lymphocytes spontaneously entered G/M of the cell cycle and died by apoptosis by 24 h post-culture, regardless of BLV infection or PL status. The spontaneous proliferation that characterizes PL cattle was primarily due to a small population of surviving B lymphocytes, but T lymphocytes also contributed. Viral protein expression was detectable in only 5–15% of cultured PBMC from PL cattle and the majority of these lymphocytes were delayed in cell cycle and spared from apoptosis. Unexpectedly, we determined that only 3% of the spontaneously proliferating lymphocytes expressed viral proteins. Previous reports show that spontaneous proliferation decreases when virus expression is suppressed. Together with our results, this suggests that virus expression by one population of B lymphocytes promotes proliferation of another population of B lymphocytes that does not express virus. This may be due to an effect of virus on CD4 T lymphocytes, as depletion of CD4 T lymphocytes significantly decreased spontaneous proliferation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-4-971
2000-04-01
2020-01-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/4/0810971a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-4-971&mimeType=html&fmt=ahah

References

  1. Akagi, T., Ono, H. & Shimotohno, K. ( 1996; ). Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21Waf1/Cip1/Sdi1. Oncogene 12, 1645-1652.
    [Google Scholar]
  2. Ayyavoo, V., Mahboubi, A., Mahalingam, S., Ramalingam, R., Kudchodkar, S., Williams, W. V., Green, D. R. & Weiner, D. B. ( 1997; ). HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B. Nature Medicine 3, 1117-1123.[CrossRef]
    [Google Scholar]
  3. Baliga, V. & Ferrer, J. F. ( 1977; ). Expression of the bovine leukemia virus and its internal antigen in blood lymphocytes. Proceedings of the Society of Experimental Biology and Medicine 156, 388-391.[CrossRef]
    [Google Scholar]
  4. Bartz, S. R., Rogel, M. E. & Emerman, M. ( 1996; ). Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control. Journal of Virology 70, 2324-2331.
    [Google Scholar]
  5. Bendixen, H. J. ( 1965; ). Bovine enzootic leukosis. Advances in Veterinary Science 10, 129-204.
    [Google Scholar]
  6. Bissonnette, N. & Hunting, D. J. ( 1998; ). p21-induced cycle arrest in G1 protects cells from apoptosis induced by UV-irradiation or RNA polymerase II blockage. Oncogene 16, 3461-3469.[CrossRef]
    [Google Scholar]
  7. Burny, A., Bruck, C., Cleuter, Y., Couez, D., Deschamps, J., Ghysdael, J., Gregoire, D., Kettmann, R., Mammerickx, M., Marcaix, G. & Portetelle, D. ( 1985; ). Bovine leukemia virus: a new mode of leukemogenesis. In Bovine Leukemia Virus, pp. 35-55. Edited by G. Klein. New York: Raven Press.
  8. Burny, A., Cleuter, Y., Kettmann, R., Mammerickx, M., Portetelle, D., Van Den Broeke, A., Willems, L. & Thomas, R. ( 1988; ). Bovine leukemia: facts and hypotheses derived from the study of an infectious cancer. Advances in Veterinary Science and Comparative Medicine 32, 149-170.
    [Google Scholar]
  9. Copeland, K. F., Haaksma, A. G., Goudsmit, J., Krammer, P. H. & Heeney, J. L. ( 1994; ). Inhibition of apoptosis in T cells expressing human T cell leukemia virus type I Tax. AIDS Research and Human Retroviruses 10, 1259-1268.[CrossRef]
    [Google Scholar]
  10. Darzynkiewicz, Z., Li, X., Gong, J., Hara, S. & Traganos, F. ( 1995; ). Analysis of cell death by flow cytometry. In Cell Growth and Apoptosis: A Practical Approach, pp. 143-167. Edited by G. P. Studzinski. New York: Oxford University Press.
  11. Depelchin, A., Letesson, J. J., Lostrie-Trussart, N., Mammerickx, M., Portetelle, D. & Burny, A. ( 1989; ). Bovine leukemia virus (BLV)-infected B-cells express a marker similar to the CD5 T cell marker. Immunology Letters 20, 69-76.[CrossRef]
    [Google Scholar]
  12. Dequiedt, F., Cantor, G. H., Hamilton, V. T., Pritchard, S. M., Davis, W. C., Kerkhofs, P., Burny, A., Kettmann, R. & Willems, L. ( 1999; ). Bovine leukemia virus-induced persistent lymphocytosis in cattle does not correlate with increased ex vivo survival of B lymphocytes. Journal of Virology 73, 1127-1137.
    [Google Scholar]
  13. DiGiacomo, R. F. ( 1992; ). The epidemiology and control of bovine leukemia virus infection. Veterinary Medicine 87, 248-277.
    [Google Scholar]
  14. Dijilali, S., Parodi, A. & 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.[CrossRef]
    [Google Scholar]
  15. Ensoli, B., Barillari, G., Salahuddin, S. Z., Gallo, R. C. & Wong-Staal, F. ( 1990; ). Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients. Nature 345, 84-86.[CrossRef]
    [Google Scholar]
  16. Ensoli, B., Buonaguro, L., Barillari, G., Fiorelli, V., Gendelman, R., Morgan, R. A., Wingfield, P. & Gallo, R. C. ( 1993; ). Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. Journal of Virology 67, 277-287.
    [Google Scholar]
  17. Fossum, C., Burny, A., Portetelle, D., Mammerickx, M. & Morein, B. ( 1988; ). Detection of B and T cells, with lectins or antibodies, in healthy and bovine leukemia virus-infected cattle. Veterinary Immunology and Immunopathology 18, 269-278.[CrossRef]
    [Google Scholar]
  18. Gaynor, E. M., Mirsky, M. L. & Lewin, H. A. ( 1996; ). Use of flow cytometry and RT–PCR for detecting gene expression by single cells. Biotechniques 21, 286-291.
    [Google Scholar]
  19. Goh, W. C., Rogel, M. E., Kinsey, C. M., Michael, S. F., Fultz, P. N., Nowak, M. A., Hahn, B. H. & Emerman, M. ( 1998; ). HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nature Medicine 4, 65-71.[CrossRef]
    [Google Scholar]
  20. Gorospe, M., Cirielli, C., Wang, X., Seth, P., Capogrossi, M. C. & Holbrook, N. J. ( 1997; ). p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells. Oncogene 14, 929-935.[CrossRef]
    [Google Scholar]
  21. He, J., Choe, S., Walker, R., Di Marzio, P., Morgan, D. O. & Landau, N. R. ( 1995; ). Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. Journal of Virology 69, 6705-6711.
    [Google Scholar]
  22. Hopkins, S. G. & DiGiacomo, R. F. ( 1997; ). Natural transmission of bovine leukemia virus in dairy and beef cattle. Veterinary Clinical North American Food Animal Practice 13, 107-128.
    [Google Scholar]
  23. Itoyama, Y., Minato, S., Kira, J., Goto, I., Sato, H., Okochi, K. & Yamamoto, N. ( 1988; ). Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy. Neurology 38, 1302-1307.[CrossRef]
    [Google Scholar]
  24. Jensen, W. A., Sheehy, S. E., Fox, M. H., Davis, W. C. & Cockerell, G. L. ( 1990; ). In vitro expression of bovine leukemia virus in isolated B-lymphocytes of cattle and sheep. Veterinary Immunology and Immunopathology 26, 333-342.[CrossRef]
    [Google Scholar]
  25. Jensen, W. A., Vicks-Beard, B. J. & Cockerell, G. L. ( 1992; ). Inhibition of protein kinase C results in decreased expression of bovine leukemia virus. Journal of Virology 66, 4427-4433.
    [Google Scholar]
  26. Jones, T. I., Barnett, L. & Lafrenz, D. ( 1994; ). Alteration of cell cycle kinetics and immunoglobulin gene transcription as the result of multiple agonist stimulation of murine B cells. Cellular Immunology 155, 156-168.[CrossRef]
    [Google Scholar]
  27. Jowett, J. B., Planelles, V., Poon, B., Shah, N. P., Chen, M. L. & Chen, I. S. ( 1995; ). The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2+M phase of the cell cycle. Journal of Virology 69, 6304-6313.
    [Google Scholar]
  28. Kenyon, S. J. & Piper, C. E. ( 1977a; ). Cellular basis of persistent lymphocytosis in cattle infected with bovine leukemia virus. Infection and Immunity 16, 891-897.
    [Google Scholar]
  29. Kenyon, S. J. & Piper, C. E. ( 1977b; ). Properties of density gradient-fractionated peripheral blood leukocytes from cattle infected with bovine leukemia virus. Infection and Immunity 16, 898-903.
    [Google Scholar]
  30. Kumar, S. P., Paul, P. S., Pomeroy, K. A., Johnson, D. W., Muscoplat, C. C., Van Der Maaten, M. J., Miller, J. M. & Sorensen, D. K. ( 1978; ). Frequency of lymphocytes bearing Fc receptors and surface membrane immunoglobulins in normal, persistent lymphocytotic and leukemia cows. American Journal of Veterinary Research 39, 45-49.
    [Google Scholar]
  31. Lal, R. B. & Rudolph, D. L. ( 1991; ). Constitutive production of interleukin-6 and tumor necrosis factor-alpha from spontaneously proliferating T cells in patients with human T-cell lymphotropic virus type-I/II. Blood 78, 571-574.
    [Google Scholar]
  32. Lal, R. B., Hjelle, B. & Rudolph, D. L. ( 1992; ). Spontaneous proliferation of HTLV-II-infected peripheral blood lymphocytes: HLA-DR-driven, IL-2-dependent response. Microbiological Immunology 36, 865-872.[CrossRef]
    [Google Scholar]
  33. Li, C. J., Friedman, D. J., Wang, C., Metelev, V. & Pardee, A. B. ( 1995; ). Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science 268, 429-431.[CrossRef]
    [Google Scholar]
  34. Li, C. J., Ueda, Y., Shi, B., Borodyansky, L., Huang, L., Li, Y. Z. & Pardee, A. B. ( 1997; ). Tat protein induces self-perpetuating permissivity for productive HIV-1 infection. Proceedings of the National Academy of Sciences, USA 94, 8116-8120.[CrossRef]
    [Google Scholar]
  35. Lindholm, P. F., Marriott, S. J., Gitlin, S. D., Bohan, C. A. & Brady, J. N. ( 1990; ). Induction of nuclear NF-kappa B DNA binding activity after exposure of lymphoid cells to soluble tax1 protein. New Biologist 2, 1034-1043.
    [Google Scholar]
  36. Luciw, P. A. & Leung, N. J. ( 1994; ). Mechanisms of retrovirus replication. In The Retroviridae, pp. 159-298. Edited by J. A. Levy. New York: Plenum Press.
  37. Mann, D. A. & Frankel, A. D. ( 1991; ). Endocytosis and targeting of exogenous HIV-1 Tat protein. EMBO Journal 10, 1733-1739.
    [Google Scholar]
  38. Mann, D. L., Martin, P., Hamlin-Green, G., Nalewaik, R. & Blattner, W. ( 1994; ). Virus production and spontaneous cell proliferation in HTLV-I-infected lymphocytes. Clinical Immunology and Immunopathology 72, 312-320.[CrossRef]
    [Google Scholar]
  39. Marriott, S. J., Lindholm, P. F., Reid, R. L. & Brady, J. N. ( 1991; ). Soluble HTLV-I Tax1 protein stimulates proliferation of human peripheral blood lymphocytes. New Biologist 3, 678-686.
    [Google Scholar]
  40. Marriott, S. J., Trinh, D. & Brady, J. N. ( 1992; ). Activation of interleukin-2 receptor alpha expression by extracellular HTLV-I Tax1 protein: a potential role in HTLV-I pathogenesis. Oncogene 7, 1749-1755.
    [Google Scholar]
  41. Mirsky, M. L., Da, Y. & Lewin, H. A. ( 1993; ). Detection of bovine leukemia virus proviral DNA in individual cells. PCR Methods and Applications 2, 333-340.[CrossRef]
    [Google Scholar]
  42. Mirsky, M. L., Olmstead, C. A., Da, Y. & Lewin, H. A. ( 1996; ). The prevalence of proviral bovine leukemia virus in peripheral blood mononuclear cells at two subclinical stages of infection. Journal of Virology 70, 2178-2183.
    [Google Scholar]
  43. Muscoplat, C. C., Alhaji, I., Johnson, D. W., Pomeroy, K. A., Olson, J. M., Larson, V. L., Stevens, J. B. & Sorensen, D. K. ( 1974; ). Characteristics of lymphocyte responses to phytomitogens: comparison of responses of lymphocytes from normal and lymphocytotic cows. American Journal of Veterinary Research 35, 1053-1055.
    [Google Scholar]
  44. Prince, H. E., Lee, H., Jensen, E. R., Swanson, P., Weber, D., Fitzpatrick, L., Doyle, M. & Kleinman, S. ( 1991a; ). Immunologic correlates of spontaneous lymphocyte proliferation in human T-lymphotropic virus infection. Blood 78, 169-174.
    [Google Scholar]
  45. Prince, H. E., Weber, D. M. & Jensen, E. R. ( 1991b; ). Spontaneous lymphocyte proliferation in HTLV-I/II infection reflects preferential activation of CD8 and CD16/56 cell subsets. Clinical Immunology and Immunopathology 58, 419-430.[CrossRef]
    [Google Scholar]
  46. Richardson, J. H., Hollsberg, P., Windhagen, A., Child, L. A., Hafler, D. A. & Lever, A. M. ( 1997; ). Variable immortalizing potential and frequent virus latency in blood-derived T-cell clones infected with human T-cell leukemia virus type I. Blood 89, 3303-3314.
    [Google Scholar]
  47. Sagata, N., Yasanuga, T., Tsuzuku-Kawamura, J., Ohihi, K., Ogawa, Y. & Ihawa, I. ( 1985; ). Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proceedings of the National Academy of Sciences, USA 82, 677-682.[CrossRef]
    [Google Scholar]
  48. Spinozzi, F., Pagliacci, M. C., Agea, E., Migliorati, G., Riccardi, C., Bertotto, A. & Nicoletti, I. ( 1995; ). Protein tyrosine kinase inhibition and cell proliferation: is the [3H]-thymidine uptake assay representative of the T-lymphocyte proliferation rate? Journal of Investigational Allergology & Clinical Immunology 5, 91-96.
    [Google Scholar]
  49. Stone, D. M., McElwain, T. F. & Davis, W. C. ( 1994; ). Enhanced B-lymphocyte expression of IL-2R alpha associated with T lymphocytosis in BLV-infected persistently lymphocytotic cows. Leukemia 8, 1057-1061.
    [Google Scholar]
  50. Stone, D. M., Hof, A. J. & Davis, W. C. ( 1995; ). Up-regulation of IL-2 receptor alpha and MHC class II expression on lymphocyte subpopulations from bovine leukemia virus infected lymphocytotic cows. Veterinary Immunology and Immunopathology 48, 65-76.[CrossRef]
    [Google Scholar]
  51. Stone, D. M., Norton, L. K., Magnuson, N. S. & Davis, W. C. ( 1996; ). Elevated pim-1 and c-myc proto-oncogene induction in B lymphocytes from BLV-infected cows with persistent B lymphocytosis. Leukemia 10, 1629-1638.
    [Google Scholar]
  52. Stone, D. M., Norton, L. K. & Davis, W. C. ( 1997; ). Modulation of bovine leukemia virus-associated spontaneous lymphocyte proliferation by monoclonal antibodies to lymphocyte surface molecules. Clinical Immunology and Immunopathology 83, 156-164.[CrossRef]
    [Google Scholar]
  53. Takashima, I., Olson, C., Driscoll, D. M. & Baumgartener, L. E. ( 1977; ). B-lymphocytes and T-lymphocytes in three types of bovine lymphosarcoma. Journal of the National Cancer Institute 59, 1205-1209.
    [Google Scholar]
  54. Thorn, R. M., Gupta, R., Kenyon, S. J. & Ferrer, J. F. ( 1981; ). Evidence that the spontaneous blastogenesis of lymphocytes from bovine leukemia virus-infected cattle is viral antigen specific. Infection and Immunity 34, 84-89.
    [Google Scholar]
  55. Tough, D. F. & Sprent, J. (1996). Measurement of T and B cell turnover with bromodeoxyuridine. In Current Protocols in Immunology, pp. 4.7.1–4.7.6. Edited by J. E. Coligan, A. M. Kruisbeek, D. H. Margulie, E. M. Shevac & W. Strobe. New York: John Wiley and Sons.
  56. Trueblood, E. S., Brown, W. C., Palmer, G. H., Davis, W. C., Stone, D. M. & McElwain, T. F. ( 1998; ). B-lymphocyte proliferation during bovine leukemia virus-induced persistent lymphocytosis is enhanced by T-lymphocyte-derived interleukin-2. Journal of Virology 72, 3169-3177.
    [Google Scholar]
  57. Uchiyama, T. ( 1997; ). Human T cell leukemia virus type I (HTLV-I) and human diseases. Annual Review of Immunology 15, 15-37.[CrossRef]
    [Google Scholar]
  58. Williams, D. L., Amborski, G. F. & Davis, W. C. ( 1988; ). Enumeration of T and B lymphocytes in bovine leukemia virus-infected cattle, using monoclonal antibodies. American Journal of Veterinary Research 49, 1098-1103.
    [Google Scholar]
  59. Yao, X. J., Mouland, A. J., Subbramanian, R. A., Forget, J., Rougeau, N., Bergeron, D. & Cohen, E. A. ( 1998; ). Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells. Journal of Virology 72, 4686-4693.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-4-971
Loading
/content/journal/jgv/10.1099/0022-1317-81-4-971
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error