Impact de molécules antivirales contre l'infection à CytoMégaloVirus humaindans des modèles cellulaires et placentaires

Abstract : The human cytomegalovirus (HCMV) is a worldwide common virus involved in diseases in immunocompromised patients, and in congenital infection. Few treatments. Antiviral drugs are limited, not devoid of toxicity, and so cannot be administered to pregnant women. Moreover, they promote the emergence of resistance mutations. Development of new therapies is necessary, also a better understanding of the mechanisms of HCMV infection during pregnancy. In this work, we used different models of viral infection; first in vitro, in order to test new potential antiviral molecules targeting the cyclooxygenase 2 enzyme, which is involved in the inflammation process; secondly an ex vivo model, on first and third trimester placental explants. We also studied the expression profile of inflammatory cytokines induced by the HCMV infection in this model.We have tested new cyclooxygenase 2 inhibitors in vitro. Within them, RG193 shows a synergistic effect with the maribavir and baicalein, which is promising for potential dual therapy. Concerning the ex vivo culture model, we could demonstrate the viability of explants and antiviral efficacy of various molecules on HCMV infection. Preliminary results on the expression of cytokines in infected placentas show differences between first and third trimester of pregnancy. However, antiviral tested appear to have little impact on the regulation of proinflammatory cytokines MCP-1, TNF- α, IP-10 mRNA during infection.
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Deborah Andouard. Impact de molécules antivirales contre l'infection à CytoMégaloVirus humaindans des modèles cellulaires et placentaires. Médecine humaine et pathologie. Université de Limoges, 2015. Français. ⟨NNT : 2015LIMO0069⟩. ⟨tel-01333745⟩

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