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Evaluation du potentiel antiviral de nouvelles molécules dans des modèles cellulaires et tissulaires d'infection à cytomégalovirus humain

Abstract : Human Cytomegalovirus (HCMV) infection is a major matter of public health concern. Current treatments against HCMV infection are effective but frequently toxic, therefore proscribed during pregnancy. In order to have highly performing and reliable tools to evaluate the new treatments on the pre-clinic phase, particularly in the context of HCMV congenital infection, we have developed antiviral models using strains with tropism towards the endothelium over different cell types. Additionally, we optimized two models: 1) the ex vivo model of placental villi cell culture, allowing the evaluation of treatments within a complex tissue. 2) The in vivo model in humanized mice by transplanting human placental explants to assess the antiviral efficacy, keeping in mind the strict species specificity of HCMV.Using the developed in vitro and ex vivo models, we evaluated three new therapeutic approaches: A model molecule with a cellular target derived from artesunate and a new cidofovir analogue of low toxicity, to assess their therapeutic potential; and an immunologic approach using hyper-immunoglobulins with high neutralizing capacity, to better understand their mode of action at the placental level. Therefore, this thesis work is placed within the context of the evaluation of new antiviral molecules to improve the treatment of HCMV infection.
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Chloé Jacquet. Evaluation du potentiel antiviral de nouvelles molécules dans des modèles cellulaires et tissulaires d'infection à cytomégalovirus humain. Médecine humaine et pathologie. Université de Limoges, 2019. Français. ⟨NNT : 2019LIMO0080⟩. ⟨tel-03510302⟩

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