References of "Willems, Luc"
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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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See detailIn Vitro And In Vivo Oncogenic Potential Of Bovine Leukemia Virus G4 Protein
Kerkhofs, P.; Heremans, H.; Burny, A. et al

in Journal of Virology (1998), 72(3),

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See detailPhosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.
Willems, Luc ULg; Grimonpont, Cathy; Kerkhofs, Pierre et al

in Oncogene (1998), 16(17), 2165-76

The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a ... [more ▼]

The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a model for the Human T-cell leukemia virus type I (HTLV-I), Bovine Leukemia Virus (BLV) permits the characterization of viral replication and leukemogenesis in vivo. Here, we show that the BLV Tax protein is phosphorylated on serine residues 106 and 293 both in insect and in mammalian cells. These sites can also be efficiently phosphorylated by the cdc2 and MAP kinases in vitro. Mutation of these residues does not affect the capacity of the Tax protein to function as a transactivator. Indeed, the Tax proteins mutated at one or both serines increase LTR-directed viral transcription at levels similar to those obtained with wild-type Tax in cell culture. Moreover, inhibition of Tax phosphorylation by W7, a calmodulin antagonist, does not alter its transactivation activity. Thus, phosphorylation on serines 106 and 293 is not required for transactivation by Tax. However, simultaneous substitution of both serines into alanine residues destroys the capacity of Tax to cooperate with the Ha-ras oncogene to transform primary rat embryo fibroblasts and induce tumors in nude mice. When the serines were replaced with aspartic acid residues, the oncogenic potential of Tax was maintained indicating that the negative charge rather than the phosphate group itself was required for Tax oncogenicity. Finally, to assess the role of the serine residues in vivo, recombinant viruses which express the Tax mutants were constructed and injected into sheep. It appeared that the mutated proviruses replicate at levels similar to the wild-type virus in vivo. We conclude that Tax phosphorylation is dispensable for transactivation and viral replication in vivo but is required for its oncogenic potential in vitro. [less ▲]

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See detailMutations in the immunosuppressive peptide of bovine leukema virus affect fusion and infectivity in vivo
GATOT, Jean-Stéphane ULg; Kettmann, Richard ULg; Callebaut-Mornon, Isabelle et al

in Virus Research (1997), 47(2-Special Issue), 103

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See detailThe Cloning And Sequencing Of An Ovine C-Myc Cdna
Kiermer, V.; Dequiedt, Franck ULg; Masengo, R. et al

in DNA Sequence : The Journal of DNA Sequencing & Mapping (1997), 7(3-4),

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See detailThe Major Homology Region Of Bovine Leukaemia Virus P24(Gag) Is Required For Virus Infectivity In Vivo
Willems, Luc ULg; Kerkhofs, P.; Attenelle, L. et al

in Journal of General Virology (1997), 78

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See detailPhosphorylation of the Bovine Leukemia Virus transactivator p34Tax is required for transformation but not for transactivation.
Kettmann, Richard ULg; Grimonpont, C.; Kerkhofs, Pierre et al

in FASEB Journal (1997), 11(9), 1179

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See detailBovine Herpesvirus 1-Induced Apoptosis Occurs At The G0/G1 Phase Of The Cell Cycle
Hanon, Emilien ULg; Hoornaert, S.; Dequiedt, Franck ULg et al

in Virology (1997), 232(2), 351-358

We have previously shown that bovine herpesvirus 1 (BHV-1), even when inactivated, induces apoptotic cell death in mitogen-stimulated bovine peripheral blood mononuclear cells (PBMCs) (Hanon et al., 1996 ... [more ▼]

We have previously shown that bovine herpesvirus 1 (BHV-1), even when inactivated, induces apoptotic cell death in mitogen-stimulated bovine peripheral blood mononuclear cells (PBMCs) (Hanon et al., 1996, J. Virol. 70, 4116-4120). In order to gain insight into this process, we have investigated the cell cycle phase at which BHV-1 induces apoptosis in PBMCs. Our results show that the percentage of cells that progress through the S phase was always lower in BHV-1-infected PBMCs than in control cells. This effect was not due to a defective activation of mitogen-stimulated PBMCs since BHV-1 only slightly affected the percentage of cells expressing BoCD25, a well-known lymphocyte activation marker. Furthermore, mimosine and cyclosporine A, two chemicals that inhibit entry into the S phase of the cell cycle by different pathways, did not affect the ability of BHV-1 to induce apoptosis. BHV-1-induced apoptosis also occurred in unstimulated PBMCs and interestingly, this was associated with the expression of c-myc and BoCD25 proteins both of which are related to cell cycle progression. All together, these data provide evidence demonstrating that BHV-1-induced apoptosis occurs at the G0/G1 phase of the cell cycle. [less ▲]

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