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See detailDiscordance between bovine leukemia virus tax immortalization in vitro and oncogenicity in vivo.
Twizere, Jean-Claude ULiege; 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 detailAlteration of thyroid hormones, insulin-like growth factor-I (IGF-I) and IGFBPs in finishing calves treated with dexamethasone
Bertozzi, Carlo; Massart, Serge; Darras, Veerle et al

in Canadian Journal of Animal Science (2000), 80

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See detailSélection assistée par marqueurs génétiques en spéculation laitière.
Parmentier, Isabelle; Renaville, Robert ULiege; Gengler, Nicolas ULiege et al

in 3ème Carrefour des Productions Animales: Les biotechnologies: enjeu de société ? (1998, January)

Introduction L'axe somatotrope joue un rôle central dans le contrôle de la régulation des productions animales en général et de la production laitière en particulier. La mise en évidence de marqueurs ... [more ▼]

Introduction L'axe somatotrope joue un rôle central dans le contrôle de la régulation des productions animales en général et de la production laitière en particulier. La mise en évidence de marqueurs génétiques, au niveau de cet axe, associés à des facteurs quantitatifs et qualitatifs de production laitière devrait réduire les coûts des programmes de sélection appliqués à ce jour et mieux les orienter. En conséquence, notre projet a pour objectif principal d'étudier les variations génétiques des gènes codant pour la protéine Pit-1 et pour le récepteur à l'hormone de croissance (GHR), intervenant au niveau de l'axe somatotrope, et de mettre en relation ces variations avec certaines caractéristiques de production laitière chez les bovins [less ▲]

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See detailPhosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.
Willems, Luc ULiege; 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 detailGrowth hormone binding protein (GHBP) during lactation in cows
Renaville, Robert ULiege; Prandi, Alberto; Massart, Serge et al

in Archivio Veterinario Italiano (1998), 48

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See detailInsulin-like growth factor-I (IGF-I), IGF-binding proteins synthesis, and thyroid status are affected by dexamethasone esters treatment in finishing calves
Bertozzi, Carlo; Massart, Serge; Prandi, Alberto et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (1998), 2(special issue), 45

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See detailEmpreintes génétiques et certification en production bovine.
Mortiaux, Frédéric; Renaville, Robert ULiege; Peelman, Luc et al

in 3° Carrefour des Productions Animales (1998)

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See detailRelations entre le polymorphisme de gène Pit-1 et le potentiel génétique de taureaux Holstein
Renaville, Robert ULiege; Gengler, Nicolas ULiege; Prandi, Alberto et al

in Deuxieme Carrefour des productions animales: la filiere lait. (1997, January 22)

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See detailPolymorphisme au niveau du récepteur de l’hormone de croissance et production laitière
Renaville, Robert ULiege; Gengler, Nicolas ULiege; Prandi, Alberto et al

in Deuxieme Carrefour des productions animales: la filiere lait. (1997, January 22)

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

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

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See detailOrigine des produits animaux et empreinte génétique
Portetelle, Daniel ULiege; Mortiaux, Frédéric; Burny, Arsène et al

in Agricontact (1997), 294

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See detailPit-1 gene HinfI RFLP and growth traits in double-muscled Belgian Blue cattle
Renaville, Robert ULiege; Gengler, Nicolas ULiege; Parmentier, Isabelle et al

in Journal of Animal Science (1997), 75(1), 146

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

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

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See detailCertification in the meat channel.
Mortiaux, Frédéric; Renaville, Robert ULiege; Gengler, Nicolas ULiege et al

in Journal of Animal Science (1997), 75(1), 136

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See detailLe typage génétique: un outil de certification en production bovine
Mortiaux, Frédéric; Renaville, Robert ULiege; Parmentier, Isabelle et al

Conference (1997)

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See detailImmunological effect of a synthetic growth hormone peptide on IGF-I and IGFBPs in growing pigs
Renaville, Robert ULiege; Bertozzi, Carlo; Carelli, Claude et al

in 4th Intern. Symp. Insulin-like Growth Factors (1997)

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See detailVariation des IGFBPs au cours de la lactation
Massart, Serge; Renaville, Robert ULiege; Bertozzi, Carlo et al

in 2° Carrefour des Productions Animales (1997)

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