Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1996 Apr;70(4):2178–2183. doi: 10.1128/jvi.70.4.2178-2183.1996

The prevalence of proviral bovine leukemia virus in peripheral blood mononuclear cells at two subclinical stages of infection.

M L Mirsky 1, C A Olmstead 1, Y Da 1, H A Lewin 1
PMCID: PMC190056  PMID: 8642640

Abstract

The bovine leukemia virus (BLV) is an oncogenic retrovirus that is associated with the development of persistent lymphocytosis (PL) and lymphoma in cattle. While B lymphocytes have been shown to be the primary cellular target of BLV, recent studies suggest that some T lymphocytes and monocytes may be infected by the virus. Because virally altered functions of monocytes and/or T cells could contribute to the development of lymphoproliferative disease, we sought to clarify the distribution of the BLV provirus in subpopulations of peripheral blood mononuclear cells in seropositive cows with and without PL. CD2+ T cells, monocytes, and CD5+ and CD5- B cells were sorted by flow cytometry and tested for the presence of BLV by single-cell PCR. We did not obtain convincing evidence that peripheral blood monocytes or T lymphocytes contain the BLV provirus in seropositive cows with or without PL. In seropositive cows without PL (n=14), BLV-infected CD5+ and CD5- B cells accounted for 9.2% +/- 19% and 0.1% +/- 1.8% of circulating B lymphocytes, respectively. In cows with PL (n=5), BLV-infected CD5+ and CD5- B cells accounted for 66% +/- 4.8% and 13.9% +/- 6.6% of circulating B lymphocytes, respectively. The increase in lymphocyte numbers in cows with PL was entirely attributable to the 45-fold and 99-fold expansions of infected CD5+ and CD5- B-cell populations, respectively. Our results demonstrate that B cells are the only mononuclear cells in peripheral blood that are significantly infected with BLV. On the basis of the absolute numbers of infected cells in seropositive, hematologically normal animals, there appear to be differences in susceptibility to viral spread in vivo that may be under the genetic control of the host.

Full Text

The Full Text of this article is available as a PDF (242.1 KB).

Selected References

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

  1. Buehring G. C., Kramme P. M., Schultz R. D. Evidence for bovine leukemia virus in mammary epithelial cells of infected cows. Lab Invest. 1994 Sep;71(3):359–365. [PubMed] [Google Scholar]
  2. Burny A., Cleuter Y., Kettmann R., Mammerickx M., Marbaix G., Portetelle D., Van den Broeke A., Willems L., Thomas R. Bovine leukemia: facts and hypotheses derived from the study of an infectious cancer. Adv Vet Sci Comp Med. 1988;32:149–170. doi: 10.1016/b978-0-12-039232-2.50010-4. [DOI] [PubMed] [Google Scholar]
  3. CROSHAW J. E., Jr, ABT D. A., MARSHAK R. R., HARE W. C., SWITZER J., IPSEN J., DUTCHER R. M. PEDIGREE STUDIES IN BOVINE LYMPHOSARCOMA. Ann N Y Acad Sci. 1963 Nov 4;108:1193–1202. doi: 10.1111/j.1749-6632.1963.tb13444.x. [DOI] [PubMed] [Google Scholar]
  4. Criteria for the determination of the normal and leukotic state in cattle. J Natl Cancer Inst. 1968 Jul;41(1):243–263. [PubMed] [Google Scholar]
  5. Depelchin A., Letesson J. J., Lostrie-Trussart N., Mammerickx M., Portetelle D., Burny A. Bovine leukemia virus (BLV)-infected B-cells express a marker similar to the CD5 T cell marker. Immunol Lett. 1989 Jan 15;20(1):69–76. doi: 10.1016/0165-2478(89)90071-0. [DOI] [PubMed] [Google Scholar]
  6. Deschamps J., Kettmann R., Burny A. Experiments with cloned complete tumor-derived bovine leukemia virus information prove that the virus is totally exogenous to its target animal species. J Virol. 1981 Nov;40(2):605–609. doi: 10.1128/jvi.40.2.605-609.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  8. Esteban E. N., Thorn R. M., Ferrer J. F. Characterization of the blood lymphocyte population in cattle infected with the bovine leukemia virus. Cancer Res. 1985 Jul;45(7):3225–3230. [PubMed] [Google Scholar]
  9. Ferrer J. F. Bovine lymphosarcoma. Adv Vet Sci Comp Med. 1980;24:1–68. [PubMed] [Google Scholar]
  10. Ferrer J. F., Marshak R. R., Abt D. A., Kenyon S. J. Persistent lymphocytosis in cattle: its cause, nature and relation to lymphosarcoma. Ann Rech Vet. 1978;9(4):851–857. [PubMed] [Google Scholar]
  11. Gatei M. H., Brandon R. B., Naif H. M., McLennan M. W., Daniel R. C., Lavin M. F. Changes in B cell and T cell subsets in bovine leukaemia virus-infected cattle. Vet Immunol Immunopathol. 1989 Nov 30;23(1-2):139–147. doi: 10.1016/0165-2427(89)90116-5. [DOI] [PubMed] [Google Scholar]
  12. Haas L., Divers T., Casey J. W. Bovine leukemia virus gene expression in vivo. J Virol. 1992 Oct;66(10):6223–6225. doi: 10.1128/jvi.66.10.6223-6225.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hall G. A., Sopp P., Howard C. J. An investigation of temporary workshop clusters reacting with cells of the mononuclear phagocytic system. Vet Immunol Immunopathol. 1993 Nov;39(1-3):225–236. doi: 10.1016/0165-2427(93)90185-7. [DOI] [PubMed] [Google Scholar]
  14. Heeney J. L., Valli P. J., Jacobs R. M., Valli V. E. Evidence for bovine leukemia virus infection of peripheral blood monocytes and limited antigen expression in bovine lymphoid tissue. Lab Invest. 1992 May;66(5):608–617. [PubMed] [Google Scholar]
  15. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  16. Kantor A. B. The development and repertoire of B-1 cells (CD5 B cells). Immunol Today. 1991 Nov;12(11):389–391. doi: 10.1016/0167-5699(91)90136-H. [DOI] [PubMed] [Google Scholar]
  17. Kenyon S. J., Piper C. E. Cellular basis of persistent lymphocytosis in cattle infected with bovine leukemia virus. Infect Immun. 1977 Jun;16(3):891–897. doi: 10.1128/iai.16.3.891-897.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kettmann R., Cleuter Y., Mammerickx M., Meunier-Rotival M., Bernardi G., Burny A., Chantrenne H. Genomic integration of bovine leukemia provirus: comparison of persistent lymphocytosis with lymph node tumor form of enzootic. Proc Natl Acad Sci U S A. 1980 May;77(5):2577–2581. doi: 10.1073/pnas.77.5.2577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kettmann R., Marbaix G., Cleuter Y., Portetelle D., Mammerickx M., Burny A. Genomic integration of bovine leukemia provirus and lack of viral RNA expression in the target cells of cattle with different responses to BLV infection. Leuk Res. 1980;4(6):509–519. doi: 10.1016/0145-2126(80)90062-4. [DOI] [PubMed] [Google Scholar]
  20. Kettmann R., Portetelle D., Mammerickx M., Cleuter Y., Dekegel D., Galoux M., Ghysdael J., Burny A., Chantrenne H. Bovine leukemia virus: an exogenous RNA oncogenic virus. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1014–1018. doi: 10.1073/pnas.73.4.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lagarias D. M., Radke K. Transcriptional activation of bovine leukemia virus in blood cells from experimentally infected, asymptomatic sheep with latent infections. J Virol. 1989 May;63(5):2099–2107. doi: 10.1128/jvi.63.5.2099-2107.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Letesson J. J., Mager A., Mammerickx M., Burny A., Depelchin A. B cells from bovine leukemia virus- (BLV) infected sheep with hematological disorders express the CD5 T cell marker. Leukemia. 1990 May;4(5):377–379. [PubMed] [Google Scholar]
  23. Lewin H. A., Schmitt K., Hubert R., van Eijk M. J., Arnheim N. Close linkage between bovine prolactin and BoLA-DRB3 genes: genetic mapping in cattle by single sperm typing. Genomics. 1992 May;13(1):44–48. doi: 10.1016/0888-7543(92)90200-c. [DOI] [PubMed] [Google Scholar]
  24. Lewin H. A., Wu M. C., Nolan T. J., Stewart J. A. Peripheral B lymphocyte percentage as an indicator of subclinical progression of bovine leukemia virus infection. J Dairy Sci. 1988 Sep;71(9):2526–2534. doi: 10.3168/jds.S0022-0302(88)79841-0. [DOI] [PubMed] [Google Scholar]
  25. Mammerickx M., Lorenz R. J., Straub O. C., Donnelly W. J., Flensburg J. C., Gentile G., Markson L. M., Ressang A. A., Taylor S. M. Bovine hematology. III. Comparative breed studies on the leukocyte parameters of several European cattle breeds as determined in the common reference laboratory. Zentralbl Veterinarmed B. 1978 May;25(4):257–267. [PubMed] [Google Scholar]
  26. Matheise J. P., Delcommenne M., Mager A., Didembourg C. H., Letesson J. J. CD5+ B cells from bovine leukemia virus infected cows are activated cycling cells responsive to interleukin 2. Leukemia. 1992 Apr;6(4):304–309. [PubMed] [Google Scholar]
  27. Meirom R., Brenner J., Trainin Z. BLV-infected lymphocytes exhibit two patterns of expression as determined by Ig and CD5 markers. Vet Immunol Immunopathol. 1993 Mar;36(2):179–186. doi: 10.1016/0165-2427(93)90106-e. [DOI] [PubMed] [Google Scholar]
  28. Miller J. M., Miller L. D., Olson C., Gillette K. G. Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. J Natl Cancer Inst. 1969 Dec;43(6):1297–1305. [PubMed] [Google Scholar]
  29. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mirsky M. L., Da Y., Lewin H. A. Detection of bovine leukemia virus proviral DNA in individual cells. PCR Methods Appl. 1993 May;2(4):333–340. doi: 10.1101/gr.2.4.333. [DOI] [PubMed] [Google Scholar]
  31. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  32. Paul P. S., Pomeroy K. A., Johnson D. W., Muscoplat C. C., Handwerger B. S., Soper F. F., Sorensen D. K. Evidence for the replication of bovine leukemia virus in the B lymphocytes. Am J Vet Res. 1977 Jun;38(6):873–876. [PubMed] [Google Scholar]
  33. Perman V., Dirks V. A., Fangmann G., Snyder M. M., Sorensen D. K., Anderson R. K., Goltz D. J., Larson V. L., Stevens J. B. Statistical evaluation of lymphocyte values on Minnesota dairy cattle. Am J Vet Res. 1970 Jul;31(7):1217–1222. [PubMed] [Google Scholar]
  34. Romano M. J., Stewart J. A., Lewin H. A. Phenotypic characterization of bovine lymphoblastoid cell lines. Vet Immunol Immunopathol. 1989 Dec;23(3-4):293–307. doi: 10.1016/0165-2427(89)90142-6. [DOI] [PubMed] [Google Scholar]
  35. Sagata N., Yasunaga T., Tsuzuku-Kawamura J., Ohishi K., Ogawa Y., Ikawa Y. Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proc Natl Acad Sci U S A. 1985 Feb;82(3):677–681. doi: 10.1073/pnas.82.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schwartz I., Bensaid A., Polack B., Perrin B., Berthelemy M., Levy D. In vivo leukocyte tropism of bovine leukemia virus in sheep and cattle. J Virol. 1994 Jul;68(7):4589–4596. doi: 10.1128/jvi.68.7.4589-4596.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Seiki M., Eddy R., Shows T. B., Yoshida M. Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells. Nature. 1984 Jun 14;309(5969):640–642. doi: 10.1038/309640a0. [DOI] [PubMed] [Google Scholar]
  38. Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Seiki M., Hattori S., Yoshida M. Human adult T-cell leukemia virus: molecular cloning of the provirus DNA and the unique terminal structure. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6899–6902. doi: 10.1073/pnas.79.22.6899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Smith M. R., Greene W. C. Molecular biology of the type I human T-cell leukemia virus (HTLV-I) and adult T-cell leukemia. J Clin Invest. 1991 Mar;87(3):761–766. doi: 10.1172/JCI115078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sordillo L. M., Hicks C. R., Pighetti G. M. Altered interleukin-2 production by lymphocyte populations from bovine leukemia virus-infected cattle. Proc Soc Exp Biol Med. 1994 Dec;207(3):268–273. doi: 10.3181/00379727-207-43815. [DOI] [PubMed] [Google Scholar]
  42. Stone D. M., McElwain T. F., Davis W. C. Enhanced B-lymphocyte expression of IL-2R alpha associated with T lymphocytosis in BLV-infected persistently lymphocytotic cows. Leukemia. 1994 Jun;8(6):1057–1061. [PubMed] [Google Scholar]
  43. Stott M. L., Thurmond M. C., Dunn S. J., Osburn B. I., Stott J. L. Integrated bovine leukosis proviral DNA in T helper and T cytotoxic/suppressor lymphocytes. J Gen Virol. 1991 Feb;72(Pt 2):307–315. doi: 10.1099/0022-1317-72-2-307. [DOI] [PubMed] [Google Scholar]
  44. Taylor B. C., Stott J. L., Thurmond M. A., Picanso J. P. Alteration in lymphocyte subpopulations in bovine leukosis virus-infected cattle. Vet Immunol Immunopathol. 1992 Feb 15;31(1-2):35–47. doi: 10.1016/0165-2427(92)90085-5. [DOI] [PubMed] [Google Scholar]
  45. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  46. Williams D. L., Amborski G. F., Davis W. C. Enumeration of T and B lymphocytes in bovine leukemia virus-infected cattle, using monoclonal antibodies. Am J Vet Res. 1988 Jul;49(7):1098–1103. [PubMed] [Google Scholar]
  47. Williams D. L., Barta O., Amborski G. F. Molecular studies of T-lymphocytes from cattle infected with bovine leukemia virus. Vet Immunol Immunopathol. 1988 Oct;19(3-4):307–323. doi: 10.1016/0165-2427(88)90117-1. [DOI] [PubMed] [Google Scholar]
  48. Yoshida M., Hattori S., Seiki M. Molecular biology of human T-cell leukemia virus associated with adult T-cell leukemia. Curr Top Microbiol Immunol. 1985;115:157–175. doi: 10.1007/978-3-642-70113-9_11. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES