| Titre : | Inhibition de la protéine kinase PKR par les protéines L et 2A des Picornavirus |
| Auteurs : | Céline De Norre, Auteur ; Thomas Michiels, Promoteur |
| Type de document : | Travail de fin d'études |
| Editeur : | Woluwe-Saint-Lambert : Haute École Léonard de Vinci, 2024 |
| Index. décimale : | TFE - Biologie médicale |
| Mots-clés: | Picornaviridae ; Protein-Serine-Threonine kinases ; Picornain 2A ; Picornavirus ; Cardiovirus |
| Résumé : | Picornaviruses are small, non-enveloped viruses whose genome is a single-stranded RNA with positive polarity. The L protein is a small protein encoded by cardioviruses such as Theiler's virus. Activities of the L protein depend on the interaction between the L protein and RSK, but also on the C- terminal domain of the L protein. The latter interacts with FG nucleoporins. The L protein thus recruits RSK and brings it to the nuclear pores, where RSK phosphorylates FG- nucleoporins, thereby disrupting nucleocytoplasmic trafficking. L protein also inhibits the antiviral cellular kinase PKR. The aim of this project is is to test whether PKR inhibition by L is a consequence of nucleocytoplasmic traffic perturbation or whether the two activities of L are independent. In this project, we induced the disruption of nucleocytoplasmic trafficking by another way, to test whether it also triggers PKR inhibition. To this end, we used a recombinant EMCV virus expressing protease 2A of Coxsackie virus, which degrades FG-Nups and thereby triggers nucleocytoplasmic perturbation in another way. We tested whether this perturbation would lead to Fluorescence microscopy results obtained after infection of the cells with the various EMCV 2A viruses showed that nucleocytoplasmic trafficking was disrupted, as expected, after infection with wild type EMCV or with the recombinant virus expressing the 2A protease of Coxsackievirus. Western blots confirmed NUP98 phosphorylation when cells were infected with EMCV L-WT, and NUP98 cleavage when cells were infected with EMCV-2Apro. Concerning PKR, there appears to be an inhibition of PKR when cells are infected with either EMCV-2Apro or EMCV L-WT viruses suggesting a (causative?) link between nucleocytoplasmic perturbation and PKR inhibition. |
| Disponible en ligne : | Oui |
| Lieu du stage : | Institut de Duve |
| Département du TFE : | Biologie médicale |
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