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<dc:title xml:lang="fr">Etude de la dynamique spatiotemporelle des interactions VHC-récepteurs</dc:title>
<dcterms:alternative xml:lang="en">Spatiotemporal dynamics of HCV-receptors interactions</dcterms:alternative>
<dc:subject xml:lang="fr">Virus de l’hépatite C</dc:subject>
<dc:subject xml:lang="fr">Imagerie en temps réel</dc:subject>
<dc:subject xml:lang="fr">Édition génomique</dc:subject>
<dc:subject xml:lang="fr">Interaction virus-hôte</dc:subject>
<dc:subject xml:lang="fr">Occludin</dc:subject>
<dc:subject xml:lang="en">Hepatitis C virus</dc:subject>
<dc:subject xml:lang="en">Live cell imaging</dc:subject>
<dc:subject xml:lang="en">Gene editing</dc:subject>
<dc:subject xml:lang="en">Virus-host interactions</dc:subject>
<dc:subject xml:lang="en">Occludin</dc:subject>
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<tef:elementdEntree autoriteExterne="031368611" autoriteSource="Sudoc">Relations hôte-virus</tef:elementdEntree>
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<dcterms:abstract xml:lang="fr">Pour infecter les hépatocytes le virus de l'hépatite C (VHC) interagit avec de nombreux facteurs d’entrées et la dynamique d’interaction du VHC avec ces récepteurs lui permettra d’entrer dans la cellule. Parmi eux, Claudin 1 (CLDN1) et Occludin (OCLN), des protéines majeures composant les jonctions serrées (TJs). La dynamique d’interaction spatiotemporelle et ainsi que le lieu de l’interaction restent controversés. Durant ce travail de thèse j’ai utilisé l’imagerie sur cellule vivante pour étudier cette dynamique d’interaction.J’ai développé des outils biologiques pour l’imagerie et ainsi généré plusieurs lignées cellulaires exprimant à un niveau endogène l’OCLN et la CLDN1 en fusion à une étiquette et obtenue du VHC fluorescent. L’imagerie sur cellules vivantes et le suivie de particules virales uniques a démonté que l’interaction VHC-OCLN se faisait en dehors de TJs et que l’OCLN semblerait stabiliser le complexe VHC-récepteurs pour permettre son endocytose.</dcterms:abstract>
<dcterms:abstract xml:lang="en">To infect hepatocytes the hepatitis C virus (HCV) interacts with many entry factors and thedynamics of HCV interaction with these receptors lead to virus uptake. Among them,Claudin 1 (CLDN1) and Occludin (OCLN), major proteins composing the tight junctions(TJs). The dynamics of spatiotemporal interaction and the location of the interaction remainunclear and controversial. During my pHD I used live cell imaging to study spatiotemporaldynamics of HCV-receptors. I developed biological imaging tools and generated several celllines that endogenously expressed OCLN and CLDN1 fused to a fluorescent tag andlabeled HCV particles. Live cell imaging and tracking of single viral particles demonstratedthat the HCV-OCLN interaction occurs outside of TJs and that the OCLN seems to stabilizethe HCV-receptor complex to allow its uptake in the cell</dcterms:abstract>
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