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The Role of Shed GP in Ebola Virus Pathogenicity Beatriz Escudero Pérez

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The Role of Shed GP in Ebola Virus Pathogenicity Beatriz Escudero Pérez The role of shed GP in Ebola virus pathogenicity Beatriz Escudero Pérez To cite this version: Beatriz Escudero Pérez. The role of shed GP in Ebola virus pathogenicity. Virology. Ecole normale supérieure de lyon - ENS LYON, 2014. English. NNT : 2014ENSL0933. tel-01340856 HAL Id: tel-01340856 https://tel.archives-ouvertes.fr/tel-01340856 Submitted on 2 Jul 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE en vue de l'obtention du grade de Docteur de l’Université de Lyon, délivré par l’École Normale Supérieure de Lyon Discipline : Sciences de la vie Laboratoire Bases Moléculaires de la Pathogénicité Virale École Doctorale de Biologie Moléculaire, Intégrative et Cellulaire présentée et soutenue publiquement le 3 Octobre 2014 par Madame Beatriz Eugenia ESCUDERO PÉREZ _____________________________________________ The role of shed GP in Ebola virus pathogenicity ______________________________________________ Directeur de thèse : M. Viktor VOLCHKOV Devant la commission d'examen formée de : M. Renaud MAHIEUX, Centre International de Recherche en Infectiologie, Président M. Christophe PEYREFITTE, IRBA-ERL, Examinateur M. Daniel PINSCHEWER, University of Basel, Rapporteur M. Viktor VOLCHKOV, Centre International de Recherche en Infectiologie, Directeur de thèse M. Thierry WALZER, Centre International de Recherche en Infectiologie, Examinateur M. Winfried WEISSENHORN, UJF-EMBL-CNRS, Rapporteur Acknowledgments Acknowledgments I would first like to thank Professor Viktor Volchkov for having welcomed me to his laboratory and for making my dream come true: since I was eight years old I have been dreaming of working with the Ebola virus. I would specially like to thank him for his trust, which has encouraged me to be more independent within the research framework, and for his bright ability to present and organise concepts. J’aimerais aussi remercier les membres de mon jury pour m’avoir fait l’honneur d’évaluer mon travail et pour l’échange qui aura lieu le jour de ma défense: M. Peyrefitte, qui a très aimablement accepté de juger mon travail en tant que représentant de la DGA (Délégation Générale pour l’Armement), M. Walzer et M. Pinschewer et M.Weissenhorn qui ont accepté d’être les rapporteurs de ma thèse ainsi que le Professeur Mahieux, qui a accepté d’être le président de mon jury. Je tiens à remercier spécialement à Thierry Walzer pour sa totale et inconditionnelle disponibilité pour m’aider avec des doutes en immunologie et pour ses conseils professionnels. Je l´admire profondément pour son intelligence, son honnêteté, et pour sa capacité à motiver et inspirer les autres. J’aimerais aussi exprimer ma profonde gratitude aux membres de son équipe pour leur gentillesse, leur sympathie, leur disponibilité, leur soutien, leur intérêt et leur aide constante avec tout ce dont j’ai eu besoin. Je remercie en spécial à Antoine, Sophie, Fabrice et Sébastien. Un grand merci également à Armelle, avec qui j’ai passée des très bons moments ensemble et qui a réussi à m’arracher du laboratoire pour jouer au foot. Je remercie aussi à Thierry Defrance, Denis Gerlier et Mathias Faure pour leur aide désintéressée. Je les admire énormément non seulement parce qu´ils sont des grands scientifiques mais aussi parce qu´ils sont des personnes honnêtes, intelligentes et intègres. Je voudrais aussi exprimer ma plus sincère gratitude à Marc Jamin et de nouveau à Thierry Walzer pour m’avoir fait l’honneur de faire partie de mon comité de thèse il y a deux ans. Je les remercie fortement pour m’avoir aidé à 1 Acknowledgments prendre du recul sur mon projet de thèse et pour les enrichissantes discussions qui m’ont permis d’avoir un regard plus critique sur mes résultats et d´avancer dans mon projet. J’aimerais bien remercier aussi à Veronique Santyi pour sa gentillesse, sa disponibilité et pour m´avoir initiée au Biacore et l’ AKTA, machines que sans son aide, je n’aurais pas réussi à maîtriser. Je remercie également le plateau technique de cytometrie, en particulier à Sébastian et Thibault pour leur aide. Je ne peux pas non plus oublier de remercier à Renaud Colisson qui a toujours essayé de m’aider, de me faire faire des pauses pendant les intenses journées de travail et qui m’a appris patientent (même les week-ends) les bases de la cytometrie. Un grand merci aussi à tout l’équipe P4, en spécial à Audrey, pour son amabilité et son professionnalisme, à Delphine, pour sa sympathie et les bons moments passés pendant la formation, à Stephanie et à Stephan ainsi qu´au poste central de biosécurité pour m’avoir permis de réaliser toutes mes expériences dans d’excellentes conditions. Je suis très reconnaissante a la Délégation Générale pour l’Armement (DGA), La Caixa en Espagne et l’INSERM pour m´avoir permis de réaliser ce travail. Je remercie aussi à ma petite étudiante, Camille Gibourt, avec qui, malgré le fait que le temps passé ensemble fut bref, j’ai beaucoup profité de cette échange qui m´a permis de ratifier ma passion pour l’enseignement et la recherche. Un grand merci à Mathieu Mateo, qui à été mon premier maître de stage et qui m’a surtout appris dès le début l´engagement au quotidien envers la recherche. J’aimerais aussi le remercier de m´avoir soutenu et accompagné tout au long de mon stage: ses conseils, sa patience et sa facilité à expliquer des concepts pas évidents pour moi à l’époque on rendu ma première expérience au laboratoire très agréable et enrichissante. J’aimerais remercier aussi à Audrey Page, pour la confiance dont elle m´a toujours témoignée, pour s´être toujours intéressée à moi et pour avoir su garder le contact même si je ne suis pas très souvent disponible. Je remercie également à Olivier Reynard qui nous a permis 2 Acknowledgments de profiter de son large expérience dans beaucoup de domaines. Je présente aussi mes remerciements à Valentina pour avoir été ma deuxième maître de stage et m’avoir introduit au intéressant monde des GPs du virus Ebola; je la remercie également pour sa gentillesse et sa douceur qui imprègnent l´esprit du laboratoire. Même s’il n’est plus là, je tiens à remercier spécialement à Kirill Nemirov, qui est arrivé au laboratoire au même temps que moi et qui a été un énorme soutien et un très bon ami: il est une des meilleures personnes que je n’ai jamais connues. Je remercie aussi à Nicolas pour les très bons moments passés ensemble, pour sa disponibilité, ses encouragements et sa précieuse connaissance du mystérieux monde de la statistique. J’aimerais remercier à Audrey Baule, qui m’a beaucoup appris sur l’immunologie et qui a été une amie et un appui en tout moment. Je la remercie aussi pour toujours me faire confiance, pour sa compréhension et pour me pousser à élargir mes ambitions professionnelles. Sa présence au laboratoire m’a beaucoup manqué. Finalement, le plus grand remerciement est pour Philip Lawrence, qui a été mon phare dans le laboratoire depuis son arrivée. Il m`a poussé à mettre en valeur mes résultats, il m’a corrigé, écouté, recorrigé, il a toujours respecté mes opinions, il m’a défendu et il a cru en moi. Au delà des remerciements pour avoir été ma bouée professionnelle, je le remercie surtout pour avoir été un vrai ami. Je ne trouve pas assez des mots pour exprimer ma gratitude envers lui. J’adresse également mes remerciements, pour leur sympathie et leurs conseils à tous les anciens membres de l’équipe Filovirus (Sébastian, Mikel, St Patrik, Jennifer, Cidney, Ilona, Nolwen, Ludo, Amandine) ainsi qu’à nos voisins, l’équipe Pasteur. Je voudrais aussi remercier à toutes les personnes de la TOUR que j’ai croisé à un moment où à un autre et avec qui nous avons partagé des bons moments (Ludovic, Joel, Chloé…). Un grand merci aussi à mon copain Joévin, pour son inestimable soutien (je me demande encore comment il fait pour me supporter tout le temps surtout en fin de thèse), je le remercie aussi pour notre passion commune des voyages qui me rappelle qu’il y a un monde parallèle à / en dehors de la thèse que je hâte d’explorer. Merci de me rappeler de temps en temps que le travail ce n’est pas tout dans la vie et mercie de t’être toujours adapté à moi et à mes ambitions professionnelles. 3 Acknowledgments A les meves amigues Cèlia i Irene, amb qui he pogut mantenir una veritable amistat al llarg dels anys tot i la llarga distància que ens separa. Els hi agreixo molt el seu suport, la seva forma de ser i el fet que em fassin sentir que malgrat el temps que no ens veiem, encara podem comptar les unes amb les altres i compartir moments genials. També ocupades per la seva tesis, estic contenta d’haver pogut compartir aquesta difícil experiència amb elles i espero que l’acabem aviat i ens poguem veure més sovint. A Laura, por su apoyo, su alegría, su sonrisa, los viajes rélampago y su amistad. A Richard Preston, por haberme seducido con su libro Zona Caliente y haber despertado mi interés por Ebola a la temprana edad de 8 años. A toda mi familia, en especial a mis padres y a mi hermana.
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