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Isolement et caractérisation de nouvelles espèces de Torque Teno Mini Virus (TTMV) : implication potentielle dans la pathogenèse de la pneumonie

Abstract : Pneumonia is the leading cause of death in children worldwide. It can be caused by a number of known pathogens, but 15-35% of childhood pneumonia are still not associated with an etiologic agent. A pathogen discovery assay allowed us to identify new species of Torque Teno Mini Virus (TTMV, Anelloviridae), named TTMV-LY, in three undiagnosed pleural effusions from children hospitalized with parapneumonic empyema. TTMV are ubiquitous orphan viruses, and their involvement in pathogenesis remains unknown. The respiratory tract was previously described to be a site of anellovirus detection. We investigated the role of these new species in the pathogenesis of severe pneumonia.Full-length TTMV-LY genomes were isolated and in vitro replicated. The response of alveolar epithelial cells, and antigen presenting cells (APC), both involved in the inflammation process, was studied after infection with neo-synthesized virions.This study showed for the first time that: i) TTMV-LY can deeply colonize lungs, ii) alveolar epithelial cells are permissive to the TTMV-LY and allow an efficient replication, iii) viral infection modulates cellular and innate immune responses of alveolar epithelial cells, by inducing gene expression deregulations and inflammatory mediators production, iv) TTMV-LY are able to interact with APC and thereby regulate differentially their inflammatory process.All these results allowed to highlight a potential involvement of TTMV-LY in the pathogenesis of severe pneumonia and brought out the complexity of the biological mechanisms taking place during infection by viruses of this family.
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Johanna Galmès. Isolement et caractérisation de nouvelles espèces de Torque Teno Mini Virus (TTMV) : implication potentielle dans la pathogenèse de la pneumonie. Biologie cellulaire. Ecole normale supérieure de lyon - ENS LYON, 2013. Français. ⟨NNT : 2013ENSL0809⟩. ⟨tel-00923721⟩

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