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Avancées Sur La Diversité Génétique Virale Et Le Développement D’Un Système De Génétique Inverse Clément Droillard

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Avancées Sur La Diversité Génétique Virale Et Le Développement D’Un Système De Génétique Inverse Clément Droillard Origine de la pathogénicité des lagovirus : avancées sur la diversité génétique virale et le développement d’un système de génétique inverse Clément Droillard To cite this version: Clément Droillard. Origine de la pathogénicité des lagovirus : avancées sur la diversité génétique virale et le développement d’un système de génétique inverse. Microbiologie et Parasitologie. Université Rennes 1, 2020. Français. NNT : 2020REN1B016. tel-03157952 HAL Id: tel-03157952 https://tel.archives-ouvertes.fr/tel-03157952 Submitted on 3 Mar 2021 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. THESE DE DOCTORAT DE L’ UNIVERSITE DE RENNES 1 ECOLE DOCTORALE N° 600 Ecole doctorale Ecologie, Géosciences, Agronomie et Alimentation Spécialité : Microbiologie, Virologie, Parasitologie Par Clément DROILLARD ECOLE DOCTORALE N° 600 EcoleOrigine doctorale de Ecologie, la pathogénicité Géosciences, Agronomie des lagovirus et Alimentation : avancées sur la diversité Spécialité génétique : Microbiologie, virale et Virologie, le développement Parasitologie d’un système de génétique inverse Thèse présentée et soutenue à Ploufragan, le 8 septembre 2020 Par Unité de recherche : Anses Ploufragan/Plouzané/Niort, Unité Virologie, Immunologie, Parasitologie, Aviaires Clément et Cunicoles DROILLARD Rapporteurs avant soutenance : OrigineSoizick LE GUYADER de la pathogénicité Directrice de recherche, des lagovirus IFREMER, Nantes, : avancées France sur la diversité génétiquePierre Emmanuel virale CECCALDI et Professeur,le développement Université Paris-Diderot, d’un France système de génétique inverse Thèse présentée et soutenue à Ploufragan, le « date » (8) Composition du Jury : Unité de recherche : Anses Ploufragan/Plouzané/Niort, Unité Virologie, Immunologie, Parasitologie, RapporteursPrésident avantJacques soutenance LE PENDU : Directeur de recherche, CRCINA, Inserm, Nantes, France Aviaires et Cunicoles Soizick LE GUYADER Directrice de recherche, IFREMER, Nantes, France ThèsePierreExaminateurs EmmanuelN° : (10) Soizick CECCALDI LE GUYADER Professeur, UniversitéDirectrice Paris de recherche,-Diderot, France IFREMER, Nantes, France Pierre Emmanuel CECCALDI Professeur, Université Paris-Diderot, France Jacques LE SEYEC Chargé de recherche, IRSET, Rennes, France Dir. de thèse Nicolas ETERRADOSSI Directeur de recherche, ANSES, Ploufragan, France Co-dir. de thèse Ghislaine LE GALL-RECULE Chargée de projet recherche, ANSES, Ploufragan, France Composition du Jury : Remerciements Ce manuscrit est le résultat de mes trois ans de travaux de recherche effectués au sein de l’unité Virologie Immunologie Parasitologie Aviaires et Cunicoles (VIPAC) du laboratoire de Ploufragan- Plouzané-Niort de l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (Anses), sur le site de Ploufragan (Côtes d’Armor, 22). Ce travail a été possible grâce à l’aide financière de Saint-Brieuc Agglomération et du conseil départemental des Côtes d’Armor. Je tiens à remercier sincèrement Dr. Soizick Le Guyader et Pr. Pierre-Emmanuel Ceccaldi d’avoir accepté d’évaluer mon travail. Je remercie également Dr. Jacques Le Pendu et Dr. Jacques Le Seyec d’avoir accepté de faire partie de mon jury de thèse. Je remercie aussi chaleureusement les membres de mon comité de pilotage de thèse pour leur implication au bon déroulement de ce projet : Pr. Martine Bonnaure-Mallet, en qualité de tutrice, Pr. Nathalie Ruvoën-Clouet, Pr. Stephane Bertagnoli et Dr. Labib Bakkali-Kassimi. Je tiens à remercier les Drs. Gilles Salvat et Nicolas Eterradossi, en qualité de directeurs successifs de l’Anses Ploufragan, de m’avoir offert l’opportunité de travailler au sein de ce laboratoire de recherche. En qualité d’ancien chef de l’unité VIPAC et de directeur de thèse, je remercie une nouvelle fois le Dr. Nicolas Eterradossi pour son accueil dans l’unité, sa participation à l’organisation de ma thèse, ses nombreux conseils, son expertise et sa rigueur scientifique. Je tiens aussi à remercier tout particulièrement le Dr. Ghislaine Le Gall-Reculé, en qualité de co- directrice de thèse, pour sa disponibilité, sa patience, sa rigueur et sa pédagogie tout au long de la thèse. Grâce à vous j’ai appris énormément et j’ai pu mener à bien ma thèse dans d’excellentes conditions. Je remercie profondément Evelyne, qui m’a formé aux techniques de laboratoire et qui m’a aidé et soutenu tout au long de la thèse. Travailler avec toi a été une très belle expérience, tu m’as appris beaucoup pendant ces trois années, et notamment à sortir de ma zone de confort ! Je tiens à remercier encore une fois Evelyne mais aussi Paul, Céline (alias The Punisher), et Lili pour leur aide et les bons moments qu’on a passés. Merci à FX pour avoir partagé ses connaissances en bio- informatique et pour nos matchs de bad ! Merci à Chantal et à Audrey (alias La Méchante) pour nos discussions matinales. Merci à Béatrice, pour son aide et son soutien. Enfin, merci à toutes les personnes de l’unité VIPAC pour les bons moments que j’ai pu passer pendant ces trois ans de thèse. Je remercie aussi Nathan, Florian et Alexandre pour leur soutien quotidien et les bons moments que l’on a passés dans l’unité et en dehors. Merci à tous les autres doctorants de l’Anses Ploufragan que j’ai pu rencontrer pendant la thèse pour les bons moments qu’on a pu passer. Merci aux membres du SELEAC et du SPPAE pour leur disponibilité et leur participation aux phases d’expérimentation in vivo ainsi qu’au bon déroulement de celles-ci. Merci à Michel Morin et à Eric Chorin pour leur accompagnement sur le management de la qualité de thèse. Je remercie également tous les membres de l’ANSES de Ploufragan que j’ai eu à rencontrer. Pour finir, je tiens à remercier ma famille et mes amis pour leurs encouragements et leurs soutiens. Merci à toi Cindy pour ton amour, ta patience et ton soutien au cours de ces trois années de thèse. Table des matières LISTE DES ABREVIATIONS ................................................................................................................................. 1 LISTE DES FIGURES ET TABLEAUX ..................................................................................................................... 4 PRESENTATION BIBLIOGRAPHIQUE .................................................................................................................. 6 A. INTRODUCTION GENERALE ........................................................................................................................... 7 B. LES CALICIVIRUS DES LEPORIDES ................................................................................................................... 9 I. Taxonomie des Lagovirus.................................................................................................................. 9 1. Génogroupe GI .......................................................................................................................................... 11 2. Génogroupe GII ......................................................................................................................................... 11 II. Caractéristiques physico-chimiques et structurales des Lagovirus .................................................... 12 1. Morphologie ............................................................................................................................................. 12 2. Organisation génomique............................................................................................................................ 13 3. Protéines virales ........................................................................................................................................ 14 3.1. Les protéines non-structurales .......................................................................................................... 14 3.2. Les protéines structurales ................................................................................................................. 17 4. Propriétés physico-chimiques .................................................................................................................... 20 5. Résistance aux agents physico-chimiques ................................................................................................... 20 III. Cycle viral ....................................................................................................................................... 20 1. Cellules cibles ............................................................................................................................................ 20 1.1. In vitro ............................................................................................................................................. 20 1.2. In vivo .............................................................................................................................................. 21 2. Les étapes du cycle viral............................................................................................................................
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