Le parvovirus H-1 (PVH-1) est un petit virus à ADN simple brin qui se réplique de façon lytique préférentiellement dans les cellules transformées du fait de leur profil d’expression particulièrement favorable à l’activation du cycle viral. Cette caractéristique est connue sous le nom d’oncotropisme. Le génome de PVH-1 compte deux unités transcriptionnelles. La première contrôlée par le promoteur précoce P4, dont l’activation dépend de la prolifération et de la transformation cellulaires, permet l’expression des protéines non structurales NS1 et NS2, et la deuxième gouverne l’expression des protéines de capside VP1 et VP2 en réponse au promoteur P38. L’ensemble du cycle de PVH-1 dépend étroitement de la protéine NS1 qui intervient dans des processus aussi importants que la réplication de l’ADN viral, l’activation du promoteur P38 ou encore la cytotoxicité du virus. La protéine NS1 est finement régulée aussi bien au niveau trancriptionnel via le promoteur P4 dont l’activation dépend de l’état de transformation et de prolifération cellulaires, que post-traductionnel. Le but de ma thèse a été d’identifier de nouveaux éléments déterminants dans la mise en place de ces régulations et de mettre en évidence leur implication dans le cycle de vie et l’oncotropisme du PVH-1. / H 1 parvovirus (H-1PV) is a little single stranded DNA virus that preferentially replicates in a lytic manner in transformed cells due to their expression profile that meets the requirements for the activation of H¬ 1 PV life cycle unlike normal cells. This feature is known as oncotropism. H 1PV genome is constituted by two transcriptional units. The first one is driven by the proliferation and transformation dependent P4 promoter and allows the expression of both non structural proteins NS1 and NS2, and the second one controls the expression of both capsid proteins VP1 and VP2 through the activation of P38 promoter. H-1PV life cycle tightly depends on NS1 protein that is involved in crucial events, including viral DNA replication, P38 promoter activation as well as cytotoxicity.NS1 protein is regulated at both transcriptional and post translational levels.My thesis aimed at identifying new determining elements for both of these regulations and characterizing their involvement in both H-1PV life cycle and oncotropism.

H 1 parvovirus (H-1PV) is a little single stranded DNA virus that preferentially replicates in a lytic manner in transformed cells due to their expression profile that meets the requirements for the activation of H¬ 1 PV life cycle unlike normal cells. This feature is known as oncotropism. H 1PV genome is constituted by two transcriptional units. The first one is driven by the proliferation and transformation dependent P4 promoter and allows the expression of both non structural proteins NS1 and NS2, and the second one controls the expression of both capsid proteins VP1 and VP2 through the activation of P38 promoter. H-1PV life cycle tightly depends on NS1 protein that is involved in crucial events, including viral DNA replication, P38 promoter activation as well as cytotoxicity.NS1 protein is regulated at both transcriptional and post translational levels.My thesis aimed at identifying new determining elements for both of these regulations and characterizing their involvement in both H-1PV life cycle and oncotropism.