Le virus de la leucemie bovine: modele de transformation cellulaire par un retrovirus retroactivant.
1995
Lucas W.
Bovine leukemia Virus (BLV) is the etiologic agent of Enzootic Bovine Leukosis, a chronic lymphoproliferative disease of cattle. In the first part of the document, data concerning viral expression is presented. In this context, the structure of the viral Tax protein (an activator of viral expression) was analysed. Tax contains a 'zinc finger' structure and an activation domain both required for its functional activity. A CREB protein involved in the cellular regulation of viral expression was identified. The second aspect of the work concerns the oncogenic potential of the Tax protein. It was shown that Tax is able to immortalize primary cells and cooperates with the ras oncogene to transform these cells. Both Tax functions (transactivating activity and oncogenic potential) can be dissociated since several mutants unable to activate viral expression still maintain their transforming potential. The last aspect of this work involves the experimental infection of sheep as a model for the study of a viral-induced human leukemia. A new inoculation procedure using direct proviral DNA injection was developed. Using genetic engineering, genes dispensable for viral infectivity were identified and attenuated strains were obtained that can be tested as live attenuated vaccines.
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