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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Leukemia Virus, Bovine

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Disease relevance of Leukemia Virus, Bovine

  • Crude extracts from short-term cultures of lymphocytes infected with LAV bound rabbit antisera to the LAV glycoprotein gp13 (molecular weight 13,000) and the BLV proteins p24 and gp51, but did not bind antibodies to the p24 of human T-cell leukemia virus type I (HTLV-I) [1].
  • BACKGROUND: Human T-cell leukemia virus (HTLV)/bovine leukemia virus (BLV) group retroviruses, which cause hematopoietic cancers, encode a unique protein, Tax, involved in the transformation of infected cells [2].
  • In addition to these activators, the bovine leukemia virus (BLV) and the human T-cell leukemia virus (HTLV) contain alternative open reading frames (R3 and G4 for BLV; p30, p13, and p12 for HTLV) [3].
  • This activity is also neutralized when the virus is incubated with sera containing antibodies to BLV, but not when incubated with sera free of these antibodies or reference serum for the foamy-like bovine syncytial virus [4].
  • Accordingly, we showed that BLV promoter activity was induced by several deacetylase inhibitors (such as trichostatin A [TSA]) in the context of episomal LTR constructs and in the context of an integrated BLV provirus [5].

High impact information on Leukemia Virus, Bovine

  • Antiserum to LAV gp13 reacted with an ovine cell line producing BLV but also weakly with virus-free ovine cells [1].
  • In addition, 83 veterinarians, 30 leukemia patients, and 200 control human sera were tested and found negative for antibodies to the BLV [6].
  • These data demonstrate that the BLV X-LOR gene encodes a p34 transactivator product [7].
  • A major histocompatibility complex class I (BoLA-A) allele that has been previously associated with resistance to PL was associated with longevity and realization of milk production potentials, indicating that genetic resistance to PL will have an economic benefit in herds where BLV is endemic [8].
  • It was found that BLV p24 shares the common NH2-terminal proline and COOH-terminal leucine but lacks the common prolylleucylarginine tripeptide and the larger conserved region found near the NH2 terminus of all mammalian type C viral p30s [9].

Chemical compound and disease context of Leukemia Virus, Bovine

  • Cell-free preparations of BLV and density gradient-purified virus also induce syncytia when added directly to diploid embryonic lung cells and to bovine, bat, and caprine monolayer cell cultures [4].
  • Here, we show that the BLV Tax protein is phosphorylated on serine residues 106 and 293 both in insect and in mammalian cells [10].
  • Importantly, the combined mutations of these three E box motifs markedly reduced the inducibility of the BLV promoter by TSA [5].
  • Our data demonstrate that BLV expression is not correlated with the activity of protein kinase A (PKA) and is even inhibited by cyclic AMP (cAMP) [11].
  • Furthermore, a mutation of a second tyrosine residue decreased the specific binding of BLV particles to FLK cells and the capacity for viral penetration [12].

Biological context of Leukemia Virus, Bovine

  • Mechanistically, using a dominant-negative form of CREB, we showed that Tax(BLV) and HDACi synergistically activated BLV gene expression via a CREB-dependent mechanism [13].
  • These include (i) in vivo analysis of the function of mutant 21 bp sequences in transient transfection, (ii) gel mobility shift assay to show that CREB binds to BLV 21 bp repeats in vitro and (iii) the demonstration that the production of antisense CREB mRNA inhibits tax trans activation [14].
  • Since ETS proteins are known to regulate transcription of numerous retroviruses, we searched for the presence in the BLV promoter region of binding sites for PU.1/Spi-1, a B-cell- and macrophage-specific ETS family member [15].
  • These data demonstrate that CREB2 is a cellular factor able to induce BLV long terminal repeat expression in the absence of tax protein and could thus be involved in the early stages of viral infection [16].
  • PGE(2) inhibited antigen-specific PBMC stimulation, suggesting that stimulation of BLV tax and pol mRNA levels by PGE(2) is independent of cell proliferation [17].

Anatomical context of Leukemia Virus, Bovine


Gene context of Leukemia Virus, Bovine

  • Cotransfection experiments showed that the USF1 and USF2a transactivators were able to act through the BLV R region E box [21].
  • Bovine leukemia virus (BLV) p24 gene was expressed in Saccharomyces cerevisiae under the control of the PHO5 (encoding repressible acid phosphatase, rAPase) promoter [22].
  • The longest open reading frame of the BLV cell receptor gene encodes a protein containing 843 amino acids with a calculated molecular mass of 94.2 kDa which concurs with experimentally detected native BLV receptor protein [23].
  • The CREB protein thus appears to be a major transcription factor involved in BLV expression in vivo [24].
  • Small-angle X-ray diffraction experiments revealed that the SL dependence of reduction of interfilament lattice spacing is greater in BLV than in BLA and that the lattice spacing is coupled with titin-based passive tension [25].

Analytical, diagnostic and therapeutic context of Leukemia Virus, Bovine

  • The isolated BLV glycoprotein antigen did not contain ovine or bovine proteins as indicated by gel immunodiffusion [26].
  • Remarkably, chromatin immunoprecipitation assays demonstrated that HDACi treatment increased the level of CREB bound to the BLV promoter in vivo [13].
  • To examine the effects of these cytokines on BLV expression, BLV tax and pol mRNA and p24 protein were quantified by competitive PCR and immunoblotting, respectively [20].
  • These results demonstrate that vaccination with VV recombinants containing the complete env gene of BLV protects sheep against infection and that protection correlated with a CD4 T-cell response to a defined epitope [27].
  • Inhibition of deacetylation after treatment with TSA or TPX also significantly increased viral expression in PBMCs from cattle, the natural host for BLV [28].


  1. Bovine leukemia virus-related antigens in lymphocyte cultures infected with AIDS-associated viruses. Thiry, L., Sprecher-Goldberger, S., Jacquemin, P., Cogniaux, J., Burny, A., Bruck, C., Portetelle, D., Cran, S., Clumeck, N. Science (1985) [Pubmed]
  2. Defective DNA repair in cells with human T-cell leukemia/bovine leukemia viruses: role of tax gene. Philpott, S.M., Buehring, G.C. J. Natl. Cancer Inst. (1999) [Pubmed]
  3. Attenuation of bovine leukemia virus by deletion of R3 and G4 open reading frames. Willems, L., Kerkhofs, P., Dequiedt, F., Portetelle, D., Mammerickx, M., Burny, A., Kettmann, R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. Induction of syncytia by the bovine C-type leukemia virus. Diglio, C.A., Ferrer, J.F. Cancer Res. (1976) [Pubmed]
  5. Overlapping CRE and E box motifs in the enhancer sequences of the bovine leukemia virus 5' long terminal repeat are critical for basal and acetylation-dependent transcriptional activity of the viral promoter: implications for viral latency. Calomme, C., Dekoninck, A., Nizet, S., Adam, E., Nguyên, T.L., Van Den Broeke, A., Willems, L., Kettmann, R., Burny, A., Van Lint, C. J. Virol. (2004) [Pubmed]
  6. Seroepidemiologic studies on the possible relationships of human and bovine leukemia: Brief communication. Donham, K.J., VanDerMaaten, M.J., Miller, J.M., Kruse, B.C., Rubino, M.J. J. Natl. Cancer Inst. (1977) [Pubmed]
  7. The bovine leukemia virus p34 is a transactivator protein. Willems, L., Gegonne, A., Chen, G., Burny, A., Kettmann, R., Ghysdael, J. EMBO J. (1987) [Pubmed]
  8. Milk and fat yields decline in bovine leukemia virus-infected Holstein cattle with persistent lymphocytosis. Da, Y., Shanks, R.D., Stewart, J.A., Lewin, H.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. Amino-terminal sequence of bovine leukemia virus major internal protein: homology with mammalian type C virus p30 structural proteins. Oroszlan, S., Copeland, T.D., Henderson, L.E., Stephenson, J.R., Gilden, R.V. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  10. Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation. Willems, L., Grimonpont, C., Kerkhofs, P., Capiau, C., Gheysen, D., Conrath, K., Roussef, R., Mamoun, R., Portetelle, D., Burny, A., Adam, E., Lefèbvre, L., Twizere, J.C., Heremans, H., Kettmann, R. Oncogene (1998) [Pubmed]
  11. Cellular pathways involved in the ex vivo expression of bovine leukemia virus. Kerkhofs, P., Adam, E., Droogmans, L., Portetelle, D., Mammerickx, M., Burny, A., Kettmann, R., Willems, L. J. Virol. (1996) [Pubmed]
  12. The YXXL sequences of a transmembrane protein of bovine leukemia virus are required for viral entry and incorporation of viral envelope protein into virions. Inabe, K., Nishizawa, M., Tajima, S., Ikuta, K., Aida, Y. J. Virol. (1999) [Pubmed]
  13. Deacetylase inhibitors and the viral transactivator TaxBLV synergistically activate bovine leukemia virus gene expression via a cAMP-responsive element- and cAMP-responsive element-binding protein-dependent mechanism. Nguyên, T.L., Calomme, C., Wijmeersch, G., Nizet, S., Veithen, E., Portetelle, D., de Launoit, Y., Burny, A., Van Lint, C. J. Biol. Chem. (2004) [Pubmed]
  14. Member of the CREB/ATF protein family, but not CREB alpha plays an active role in BLV tax trans activation in vivo. Kiss-Toth, E., Paca-uccaralertkun, S., Unk, I., Boros, I. Nucleic Acids Res. (1993) [Pubmed]
  15. Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat. Dekoninck, A., Calomme, C., Nizet, S., de Launoit, Y., Burny, A., Ghysdael, J., Van Lint, C. Oncogene (2003) [Pubmed]
  16. A cyclic AMP-responsive DNA-binding protein (CREB2) is a cellular transactivator of the bovine leukemia virus long terminal repeat. Willems, L., Kettmann, R., Chen, G., Portetelle, D., Burny, A., Derse, D. J. Virol. (1992) [Pubmed]
  17. Prostaglandin E(2) increases bovine leukemia virus tax and pol mRNA levels via cyclooxygenase 2: regulation by interleukin-2, interleukin-10, and bovine leukemia virus. Pyeon, D., Diaz, F.J., Splitter, G.A. J. Virol. (2000) [Pubmed]
  18. Infectivity tests of secretions and excretions from cattle infected with bovine leukemia virus. Miller, J.M., Van der Maaten, M.J. J. Natl. Cancer Inst. (1979) [Pubmed]
  19. The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events. Beaufils, P., Choquet, D., Mamoun, R.Z., Malissen, B. EMBO J. (1993) [Pubmed]
  20. Regulation of bovine leukemia virus tax and pol mRNA levels by interleukin-2 and -10. Pyeon, D., Splitter, G.A. J. Virol. (1999) [Pubmed]
  21. Upstream stimulatory factors binding to an E box motif in the R region of the bovine leukemia virus long terminal repeat stimulates viral gene expression. Calomme, C., Nguyen, T.L., de Launoit, Y., Kiermer, V., Droogmans, L., Burny, A., Van Lint, C. J. Biol. Chem. (2002) [Pubmed]
  22. High yield synthesis of the bovine leukemia virus (BLV) p24 major internal protein in Saccharomyces cerevisiae. Dumont, J., Legrain, M., Portetelle, D., Brasseur, R., Burny, A., Hilger, F. Gene (1989) [Pubmed]
  23. Isolation of the missing 5'-end of the encoding region of the bovine leukemia virus cell receptor gene. Ban, J., Truong, A.T., Horion, B., Altaner, C., Burny, A., Portetelle, D., Kettmann, R. Arch. Virol. (1994) [Pubmed]
  24. Involvement of the cyclic AMP-responsive element binding protein in bovine leukemia virus expression in vivo. Adam, E., Kerkhofs, P., Mammerickx, M., Kettmann, R., Burny, A., Droogmans, L., Willems, L. J. Virol. (1994) [Pubmed]
  25. Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle. Fukuda, N., Wu, Y., Farman, G., Irving, T.C., Granzier, H. J. Physiol. (Lond.) (2003) [Pubmed]
  26. Isolation of a precipitating glycoprotein antigen from cell cultures persistently infected with bovine leukemia virus. Phillips, M., Miller, J.M., Van Der Maaten, M.J. J. Natl. Cancer Inst. (1978) [Pubmed]
  27. Protection of sheep against bovine leukemia virus (BLV) infection by vaccination with recombinant vaccinia viruses expressing BLV envelope glycoproteins: correlation of protection with CD4 T-cell response to gp51 peptide 51-70. Gatei, M.H., Naif, H.M., Kumar, S., Boyle, D.B., Daniel, R.C., Good, M.F., Lavin, M.F. J. Virol. (1993) [Pubmed]
  28. Inhibition of histone deacetylases induces bovine leukemia virus expression in vitro and in vivo. Merezak, C., Reichert, M., Van Lint, C., Kerkhofs, P., Portetelle, D., Willems, L., Kettmann, R. J. Virol. (2002) [Pubmed]
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