Archives of Virology

, Volume 160, Issue 8, pp 2087–2091 | Cite as

Delayed-onset enzootic bovine leukosis possibly caused by superinfection with bovine leukemia virus mutated in the pol gene

  • Tadaaki Watanabe
  • Emi Inoue
  • Hiroshi Mori
  • Yoshiaki Osawa
  • Katsunori OkazakiEmail author
Brief Report


Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis (EBL), to which animals are most susceptible at 4–8 years of age. In this study, we examined tumor cells associated with EBL in an 18-year-old cow to reveal that the cells carried at least two different copies of the virus, one of which was predicted to encode a reverse transcriptase (RT) lacking ribonuclease H activity and no integrase. Such a deficient enzyme may exhibit a dominant negative effect on the wild-type RT and cause insufficient viral replication, resulting in delayed tumor development in this cow.


Long Terminal Repeat Bovine Leukemia Virus Moloney Murine Leukemia Virus Reverse Transcriptase Defective Virus Enzootic Bovine Leukosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was partly supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank the workers at the Meat Inspection Office for their extensive help in collecting the samples.


  1. 1.
    Acaite J, Tamosiunas V, Lukauskas K, Milius J, Pieskus J (2007) The eradication experience of enzootic bovine leukosis from Lithuania. Prev Vet Med 82:83–89PubMedCrossRefGoogle Scholar
  2. 2.
    Burny A, Cleuter Y, Kettman R, Mammerickx M, Marbaix G, Portelle D, Van den Broeke A, Willems L, Thomas R (1998) Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer. Vet Microbiol 17:197–218CrossRefGoogle Scholar
  3. 3.
    Demirhan I, Altanerova V, Chandra A, Gerber T, Hofmann D, Altaner C, Chandra P (1996) Characterization of the RNA dependent DNA polymerase of bovine leukemia virus. Anticancer Res 16:2501–2505PubMedGoogle Scholar
  4. 4.
    Eric W, Marielle C, Antoine G, Simon W-H (1996) Clonal expansion of infected cells: a way of life for HTLV-I. J Acquir Immune Defic Syndr Hum Retrovirol 13:S92–S99CrossRefGoogle Scholar
  5. 5.
    Goff SP (2007) Retroviridae: The Retroviruses and their replication. In: Knipe DM, Howley PM, Griffin DE, Lamb RA (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1999–2069Google Scholar
  6. 6.
    Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber J, Griffiths GM, Tanaka Y, Osame M, Bangham CR (2003) Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 299:1713–1716PubMedCrossRefGoogle Scholar
  7. 7.
    Inoue E, Matsumura K, Soma N, Hirasawa S, Wakimoto M, Arakaki Y, Yoshida T, Osawa Y, Okazaki K (2013) L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus. Vet Microbiol 167:364–371PubMedCrossRefGoogle Scholar
  8. 8.
    Inoue J, Seiki M, Taniguchi T, Tsuru S, Yoshida M (1986) Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J 5:2883–2888PubMedCentralPubMedGoogle Scholar
  9. 9.
    Kahrs RF (2001) Bovine leukemia virus and enzootic bovine leucosis. Viral diseases of cattle, 2nd edn. Iowa State University Press, Ames, pp 103–112Google Scholar
  10. 10.
    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 J 8:497–503PubMedCentralPubMedGoogle Scholar
  11. 11.
    Kenyon SJ, Piper CE (1977) Cellular basis of persistent lymphocytosis in cattle infected with bovine leukemia virus. Infect Immun 16:891–897PubMedCentralPubMedGoogle Scholar
  12. 12.
    Knapen K, Kerkhofs P, Mammerickx M (1993) Eradication of enzootic bovine leukosis in Belgium: Results of the mass detection on the national cattle population in 1989, 1990 and 1991. Ann Med Vet 137:197–201Google Scholar
  13. 13.
    Moules V, Pomier C, Sibon D, Gabet AS, Reichert N, Kerkhofs P, Willems L, Mortreux F, Wattel E (2005) Fate of premalignant clones during the asymptomatic phase preceding lymphoid malignancy. Cancer Res 65:1234–1243PubMedCrossRefGoogle Scholar
  14. 14.
    Nagashima K, Yoshida M, Seiki M (1986) A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40x and two other phosphoprotein. J Virol 60:394–399PubMedCentralPubMedGoogle Scholar
  15. 15.
    Nuotio L, Rusanen H, Sihvonen L, Neuvonen E (2003) Eradication of enzootic bovine leukosis from Finland. Prev Vet Med 59:43–49PubMedCrossRefGoogle Scholar
  16. 16.
    Paul PS, Pomeroy KA, Johnson DW, Muscoplat CC, Handwerger BS, Soper FF, Sorensen DK (1977) Evidence for the replication of bovine leukemia virus in the B lymphocytes. Am J Vet Res 38:873–876PubMedGoogle Scholar
  17. 17.
    Perach M, Hizi A (1999) Catalytic features of the recombinant reverse transcriptase of bovine leukemia virus expressed in bacteria. Virology 259:176–189PubMedCrossRefGoogle Scholar
  18. 18.
    Saini SS, Allore B, Jacobs RM, Kaushik A (1999) Exceptionally long CDR3H region with multiple cysteine residues in functional bovine IgM antibodies. Eur J Immun 29:2420–2426CrossRefGoogle Scholar
  19. 19.
    Sagata N, Yasunaga T, Ohishi K, Tsuzuku-Kawamura J, Onuma M, Ikawa Y (1984) Comparison of the entire genomes of bovine leukemia virus and human T-cell leukemia virus and characterization of their unidentified open reading frames. EMBO J 3:3231–3237PubMedCentralPubMedGoogle Scholar
  20. 20.
    Straub OC (1987) Natural and experimental transmission of bovine leukemia virus. In: Burny A, Mammerickx M (eds) Enzootic bovine leucosis and bovine leukemia virus. Martinus Nijhoff Publishing, Boston, pp 229–249CrossRefGoogle Scholar
  21. 21.
    Szynal M, Cleuter Y, Beskorwayne T, Bagnis C, Van Lint C, Kerkhofs P, Burny A, Martiat P, Griebel P, Van den Broeke A (2003) Disruption of B-cell homeostatic mediated by the BLV-Tax oncoprotein: association with upregulation of Bcl-2 and signaling through NF-κB. Oncogene 22:4531–4542PubMedCrossRefGoogle Scholar
  22. 22.
    Taube R, Loya S, Avidan O, Perach M, Hizi A (1998) Reverse transcriptase of mouse mammary tumour virus: expression in bacteria, purification and biochemical characterization. Biochem J 329:579–587PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Willems L, Gegonne A, Chen G, Burny A, Kettmann R, Ghysdael J (1987) The bovine leukemia virus p34 is a transactivator protein. EMBO J 6:3385–3389PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Tadaaki Watanabe
    • 1
  • Emi Inoue
    • 1
  • Hiroshi Mori
    • 1
  • Yoshiaki Osawa
    • 1
  • Katsunori Okazaki
    • 1
    Email author
  1. 1.Laboratory of Microbiology and Immunology, Faculty of Pharmaceutical SciencesHealth Sciences University of HokkaidoIshikari-TobetsuJapan

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