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See detailSubcellular Localization Of The Bovine Leukemia Virus R3 And G4 Accessory Proteins
Lefebvre, Laurent; Ciminale, Vincenzo; Vanderplasschen, Alain ULg et al

in Journal of Virology (2002), 76(15), 7843-7854

Bovine leukemia virus (BLV) is a complex retrovirus that belongs to the Deltaretrovirus genus, which also includes Human T-cell leukemia virus type 1 (HTLV-1). Both viruses contain an X region coding for ... [more ▼]

Bovine leukemia virus (BLV) is a complex retrovirus that belongs to the Deltaretrovirus genus, which also includes Human T-cell leukemia virus type 1 (HTLV-1). Both viruses contain an X region coding for at least four proteins: Tax and Rex, which are involved in transcriptional and posttranscriptional regulation, respectively, and the accessory proteins R3 and G4 (for BLV) and p12(I), p13(II), and p30(II) (for HTLV-1). The present study was aimed at characterizing the subcellular localization of BLV R3 and G4. The results of immunofluorescence experiments on transfected HeLa Tat cells demonstrated that R3 is located in the nucleus and in cellular membranes, as previously reported for HTLV-1 p12(1). In contrast, G4, like p13(II), is localized both in the nucleus and in mitochondria. In addition, we have shown that G4 harbors a mitochondrial targeting signal consisting of a hydrophobic region and an amphipathic alpha-helix. Thus, despite a lack of significant primary sequence homology, R3 and p12(1) and G4 and p13(II) exhibit similar targeting properties, suggesting possible overlap in their functional properties. [less ▲]

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See detailLymphocyte Kinetics: The Interpretation Of Labelling Data
Asquith, B.; Debacq, C.; Macallan, Dc. et al

in Trends In Immunology (2002), 23(12),

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See detailInhibition Of Histone Deacetylases Induces Bovine Leukemia Virus Expression In Vitro And In Vivo
Merezak, C.; Reichert, M.; Van Lint, C. et al

in Journal of Virology (2002), 76(10),

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See detailIncreased Cell Proliferation, But Not Reduced Cell Death, Induces Lymphocytosis In Bovine Leukemia Virus-Infected Sheep
Debacq, C.; Asquith, B.; Kerkhofs, P. et al

in Proceedings of the National Academy of Sciences of the United States of America (2002), 99(15),

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See detailCell turnover in BLV-infected sheep
Debacq, Christophe; Peremans, T.; Kerkhofs, Pierre et al

in Aids Research and Human Retroviruses": 10th International Conference on Human Retrovirology: HTLV and Related Viruses, (2001, June)

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See detailA critical cysteine residue of bovine leukemia virus SU protein interacts with zinc and plays a role in viral infectivity.
GATOT, Jean-Stéphane ULg; Kerkhofs, Pierre; Burny, Arsène et al

in The 2001 meeting on Retroviruses. (2001, May)

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See detailCell turnover in BLV-infected sheep.
Debacq, C.; Peremans, T.; Kerkhofs, P. et al

in AIDS Research and Human Retroviruses (2001), 17(1), 13

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See detailSuboptimal Enhancer Sequences Are Required For Efficient Bovine Leukemia Virus Propagation In Vivo: Implications For Viral Latency
Merezak, C.; Pierreux, C.; Adam, E. et al

in Journal of Virology (2001), 75(15),

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See detailRole Of The Proline-Rich Motif Of Bovine Leukemia Virus Transmembrane Protein Gp30 In Viral Load And Pathogenicity In Sheep
Reichert, M.; Winnicka, A.; Willems, Luc ULg et al

in Journal of Virology (2001), 75(17),

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See detailA Multipotential Beta -1,6-N-Acetylglucosaminyl-Transferase Is Encoded by Bovine Herpesvirus Type 4
Vanderplasschen, Alain ULg; Markine-Goriaynoff, N.; Lomonte, P. et al

in Proceedings of the National Academy of Sciences of the United States of America (2000), 97(11), 5756-5761

The beta-1,6-N-acetylglucosaminyltransferase (beta1,6GnT) gene family encodes enzymes playing crucial roles in glycan synthesis. Important changes in beta1,6GnT expression are observed during development ... [more ▼]

The beta-1,6-N-acetylglucosaminyltransferase (beta1,6GnT) gene family encodes enzymes playing crucial roles in glycan synthesis. Important changes in beta1,6GnT expression are observed during development, oncogenesis, and immunodeficiency. The most characterized beta1,6GnTs in this gene family are the human (h) C2GnT-L and h-IGnT, which have core 2 [Galbeta1-->3(GlcNAcbeta1-->6)GalNAc] and I branching [GlcNAcbeta1-->3(GlcNAcbeta1-->6)Gal] activities, respectively. Recently, h-C2GnT-M was shown to be unique in forming core 2, core 4 [GlcNAcbeta1-->3(GlcNAcbeta1-->6)GalNAc], and I structures. To date, the beta1,6GnT gene family has been characterized only in mammals. Here, we describe that bovine herpesvirus type 4 (BHV-4) encodes a beta1,6GnT expressed during viral replication and exhibiting all of the core 2, core 4, and I branching activities. Sequencing of the BHV-4 genome revealed an ORF, hereafter called BORFF3-4, encoding a protein (pBORFF3-4) exhibiting 81.1%, 50.7%, and 36.6% amino acid identity with h-C2GnT-M, h-C2GnT-L, and h-IGnT, respectively. Reverse transcriptase-PCR analysis revealed that BORFF3-4 is expressed during BHV-4 replication. Expression of BORFF3-4 in Chinese hamster ovary cells directed the expression of core 2 branched oligosaccharides and I antigenic structures on the cell surface. Moreover, a soluble form of pBORFF3-4 had core 4 branching activity in addition to core 2 and I branching activities. Finally, infection of a C2GnT-negative cell line with BHV-4 induced expression of core 2 branched oligosaccharides. This study extends the beta1,6GnT gene family to a viral gene and provides a model to study the biological functions of a beta1,6GnT in the context of viral infection. [less ▲]

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See detailLong-Term Protection Against Bovine Leukaemia Virus Replication In Cattle And Sheep
Kerkhofs, P.; GATOT, Jean-Stéphane ULg; Knapen, K. et al

in Journal of General Virology (2000), 81

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See detailGenetic Determinants Of Bovine Leukemia Virus Pathogenesis
Willems, Luc ULg; Burny, A.; Collete, Delphine et al

in Aids Research and Human Retroviruses (2000), 16(16), 1787-95

The understanding of HTLV-induced disease is hampered by the lack of a suitable animal model allowing the study of both viral replication and leukemogenesis in vivo. Although valuable information has been ... [more ▼]

The understanding of HTLV-induced disease is hampered by the lack of a suitable animal model allowing the study of both viral replication and leukemogenesis in vivo. Although valuable information has been obtained in different species, such as rabbits, mice, rats, and monkeys, none of these systems was able to conciliate topics as different as viral infectivity, propagation within the host, and generation of leukemic cells. An alternate strategy is based on the understanding of diseases induced by viruses closely related to HTLV-1, like bovine leukemia virus (BLV). Both viruses indeed belong to the same subfamily of retroviruses, harbor a similar genomic organization, and infect and transform cells of the hematopoietic system. The main advantage of the BLV system is that it allows direct experimentation in two different species, cattle and sheep. [less ▲]

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See detailDiscordance between bovine leukemia virus tax immortalization in vitro and oncogenicity in vivo.
Twizere, Jean-Claude ULg; Kerkhofs, Pierre; Burny, Arsène et al

in Journal of Virology (2000), 74(21), 9895-902

Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second ... [more ▼]

Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second function, immortalization of primary cells in vitro. These activities of Tax can be dissociated on the basis of point mutations within specific regions of the protein. For example, mutation of the phosphorylation sites at serines 106 and 293 abrogates immortalization potential in vitro but maintains transcriptional activity. This type of mutant is thus particularly useful for unraveling the role of Tax immortalization activity during leukemogenesis independently of viral replication. In this report, we describe the biological properties of BLV recombinant proviruses mutated in the Tax phosphorylation sites (BLVTax106+293). Titration of the proviral loads by semiquantitative PCR revealed that the BLV mutants propagated at wild-type levels in vivo. Furthermore, two animals (sheep 480 and 296) infected with BLVTax106+293 developed leukemia or lymphosarcoma after 16 and 36 months, respectively. These periods of time are within the normal range of latencies preceding the onset of pathogenesis induced by wild-type viruses. The phenotype of the mutant-infected cells was characteristic of a B lymphocyte (immunoglobulin M positive) expressing CD11b and CD5 (except at the final stage for the latter marker), a pattern that is typical of wild-type virus-infected target cells. Interestingly, the transformed B lymphocytes from sheep 480 also coexpressed the CD8 marker, a phenotype rarely observed in tumor biopsies from chronic lymphocytic leukemia patients. Finally, direct sequencing of the tax gene demonstrated that the leukemic cells did not harbor revertant proviruses. We conclude that viruses expressing a Tax mutant unable to transform primary cells in culture are still pathogenic in the sheep animal model. Our data thus provide a clear example of the discordant conclusions that can be drawn from in vitro immortalization assays and in vivo experiments. These observations could be of interest for other systems, such as the related human T-cell leukemia virus type 1, which currently lack animal models allowing the study of the leukemogenic process. [less ▲]

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See detailProtective Effects Of A Live Attenuated Bovine Leukaemia Virus Vaccine With Deletion In The R3 And G4 Genes
Reichert, M.; Cantor, Gh.; Willems, Luc ULg et al

in Journal of General Virology (2000), 81

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See detailBovine leukemia virus as a model for human T-cell leukemia virus
Willems, Luc ULg; Burny, A.; Dangoisse, O. et al

in Current Topics in Virology (1999)

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See detailBovine Leukemia Virus-Induced Persistent Lymphocytosis In Cattle Does Not Correlate With Increased Ex Vivo Survival Of B Lymphocytes
Dequiedt, Franck ULg; Cantor, Gh.; Hamilton, Vt. et al

in Journal of Virology (1999), 73(2),

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See detailLeukemia Viruses
Burny, A.; Bex, F.; Dequiedt, Franck ULg et al

in Encyclopedia of Immunology, Academic Press (1998)

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See detailConservative Mutations In The Immunosuppressive Region Of The Bovine Leukemia Virus Transmembrane Protein Affect Fusion But Not Infectivity In Vivo
GATOT, Jean-Stéphane ULg; Callebaut, I.; Mornon, Jp. et al

in Journal of Biological Chemistry (1998), 273(21),

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