Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
Jordan Quellec, Aurélie Pédarrieu, Camille Piro-Mégy, Jonathan Barthelemy, Yannick Simonin, Sara Salinas
Ce mois-ci, c’est Florent de Montpellier qui vous propose l’article coup de coeur du ReJMiF :
« Pour cette newsletter de février, parlons de virus ! Nous allons nous pencher sur un travail réalisé par Jordan Quellec, étudiant en 3ème année de thèse à Montpellier. Son virus de cœur ? Le virus de la fièvre de la vallée du Rift (RVFV). »
Le RVFV est un virus zoonotique qui peut être transmis de l’animal (bovins, ovins) à l’Homme par l’intermédiaire de moustiques. Il est classé parmi les maladies prioritaires à étudier par l’OMS. En effet, Jordan nous indique que le taux de mortalité chez l’Homme est de 0,5 à 2%, mais peut atteindre 28% dans certains pays. Ce virus peut aussi conduire à des troubles neurologiques et c’est sur cet aspect que porte ce travail.
Jordan s’est plus particulièrement focalisé sur les astrocytes, une population de cellules du cerveau qui a de nombreuses fonctions dans le support des neurones, la régulation du métabolisme ou la réponse immunitaire. Après avoir montré que ces astrocytes peuvent être infectés et permettre la réplication du virus, il a mis en évidence que l’infection se révélait toxique pour les cellules mais retardait l’apoptose. En regardant de près les voies de l’apoptose, le virus est capable d’activer très précocement la voie des caspase 3, un marqueur de la mort cellulaire induite. Pour expliquer le retard de la mortalité cellulaire malgré une activation précoce d’une voie de l’apoptose, Jordan a montré que le virus séquestrait dans le noyau un activateur de l’apoptose via sa protéine NSs, un de ses facteurs majeurs de virulence. Mais ce n’est pas tout ! Car le virus induit également une augmentation de l’expression des gènes de la réponse inflammatoire et antivirale, au niveau de l’ARNm, mais qui ne se retrouve pas à l’échelle protéique… Pourquoi ? Tout comme pour l’apoptose, le virus est capable de séquestrer des ARNm dans le noyau, limitant la production de protéines antivirales et inflammatoires.
Ainsi, Jordan a pour la première fois mis en évidence l’infection par le RVFV d’astrocytes humains et la capacité du virus à moduler les voies d’apoptose et de la réponse immunitaire pour favoriser sa réplication.
L’article vous réserve encore d’autres secrets donc pour en savoir plus, n’hésitez pas à aller jeter un œil à son travail !
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