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Doctorat National N°De Thèse 05/19 CSVS Université Mohammed V Faculté de Médecine et de Pharmacie de Rabat Centre d’Etudes Doctorales des Sciences de la Vie et de la Santé Filière de biologie médicale, pathologie humaine et expérimentale et environnement THESE En vue de l’obtention du Doctorat National N°de thèse 05/19 CSVS Présentée et soutenue publiquement le : 03/10/2019 Par Fatima YOUSSOUFI Titre LES FACTEURS GénétiqueS de la variabilité interindividuelle de la réponse à l’inFeCtion par le vih-1 : rôle des gènes du système HLA JURY Pr M. ADNAOUI, Professeur de Médecine interne Faculté de Médecine et de Pharmacie, Université Mohammed V- Rabat Président de jury Pr S. MRANI, Professeur de Virologie, Faculté de Médecine et de Pharmacie, Université Mohammed V– Rabat Directeur de thèse Pr Y. SEKHSOKH, Professeur de Microbiologie Faculté de Médecine et de Pharmacie, Université Mohammed V- Rabat Rapporteur Pr J. ELBAKKOURI, Professeur d’Immunologie, Faculté de Médecine et de Pharmacie, Université Hassan II- Casablanca Rapporteur Pr A. BELMEKKI, Professeur d’Hématologie Faculté de Médecine et de Pharmacie, Université Mohammed V- Rabat Rapporteur Université Mohammed V Faculté de Médecine et de Pharmacie de Rabat Centre d’Etudes Doctorales des Sciences de la Vie et de la Santé Filière de biologie médicale, pathologie humaine et expérimentale et environnement THESE En vue de l’obtention du Doctorat National N°de thèse 05/19 CSVS Présentée et soutenue publiquement le : 03/10/2019 Par Fatima YOUSSOUFI Titre LES FACTEURS GénétiqueS de la variabilité interindividuelle de la réponse à l’inFeCtion par le vih-1 : rôle des gènes du système HLA JURY Pr M. ADNAOUI, Professeur de Médecine interne Faculté de Médecine et de Pharmacie, Université Mohammed V- Rabat Président de jury Pr S. MRANI, Professeur de Virologie, Faculté de Médecine et de Pharmacie, Université Mohammed V– Rabat Directeur de thèse Pr Y. SEKHSOKH, Professeur de Microbiologie Faculté de Médecine et de Pharmacie, Université Mohammed V- Rabat Rapporteur Pr J. ELBAKKOURI, Professeur d’Immunologie, Faculté de Médecine et de Pharmacie, Université Hassan II- Casablanca Rapporteur Pr A. BELMEKKI, Professeur d’Hématologie Faculté de Médecine et de Pharmacie, Université Mohammed V- Rabat Rapporteur 2 A Remerciements 3 Je tiens à exprimer tout d’abord mes remerciements aux membres du jury, Monsieur le Professeur M. ADNAOUI Merci infiniment d’avoir accepté de présider ce jury malgré votre agenda chargé. Votre énorme apport dans la prise en charge de personnes vivantes avec le VIH au Maroc est inestimable. C’est un honneur pour moi d’avoir dans ce jury un grand acteur national et international de la lutte contre le VIH/SIDA. Soyez assuré de ma gratitude. Monsieur le Professeur S.MRANI Je vous remercier pour tout le soutien que vous m’avez apporté au cours de ce travail. Je tiens à exprimer toute ma reconnaissance de m’avoir accepté sans réserve, de diriger cette thèse malgré les prérogatives qui vos tiennes et de m’avoir accueillie au sein de votre équipe, pour la confiance et la liberté que vous m’avez accordées. Monsieur le Professeur Y. SAKHSOUKH Merci Professeur pour m’avoir accueilli au sein du laboratoire LRB P3.Merci pour l’intérêt que vous avez porté à ce travail. Un grand merci d’avoir accepté de faire partie de ce jury. Je suis très honoré. Veuillez accepter mes sincères remerciements Madame le Professeur J. ELBAKKOURI Je vous remercie infiniment d’avoir accepté d’être rapporteur de cette thèse. Je suis très honoré que vous ayez bien voulu apporter à ce travail votre expertise. Merci de prendre le temps de venir à Rabat pour particper à mon jury. Je tiens à vous exprimer toute ma reconnaissance. Monsieur le Professeur A. BELMEKKI Merci pour l’intérêt que vous avez porté à ce travail. Merci d’avoir accepté de faire partie de ce jury. Je suis très honoré. Veuillez accepter mes sincères remerciements. 4 Je remercie le directeur du Centre d’Etudes Doctorales des sciences de la vie et de la santé, Monsieur le Professeur JAMAL TOUFIK Merci de m’avoir accueilli au sein de votre école doctorale et de m’avoir permis d’effectuer cette thèse dans de bonnes conditions. Je serais toujours admirative de votre rigueur scientifique, de votre créativité, de votre efficacité et de votre amour pour cette école. 5 A Mon Directeur de Thèse Monsieur le Professeur S.MRANI Directeur du Centre de Recherche de Génomique des Pathologies Humaines (GENOPATH) Je vous remercie de m'avoir accueilli au sein de vote équipe de Recherche en Virologie Moléculaire et Oncobiologie du centre GENOPATH et de m'avoir accordé la confiance et la liberté de travailler et d'évoluer. Vous m’avez apporté un grand soutien au cours de ces années passées. Je tiens à exprimer toute ma reconnaissance d'avoir accepté sans réserve, de diriger cette thèse malgré toutes vos occupations et vos responsabilités. 6 Un grand merci à Monsieur le Professeur H.EL ANNAZ Ce travail ne serait pas aussi riche et n’aurait pas pu voir le jour sans votre aide et votre encadrement, je vous remercie infiniment pour la qualité de votre encadrement exceptionnel, votre patience, votre rigueur et votre disponibilité durant ma préparation de cette thèse, vous avez toujours été là pour répondre à mes questions techniques ou scientifiques. Merci pour votre humanité et votre gentillesse en n’oubliant jamais vos petits mots d’encouragement. Je remerci Monsieur le Professeur A. LARAQUI C’est avec un grand honneur et un grand plaisir que je vous remercie. Merci infiniment pour votre encadrement, votre esprit scientifique, votre humanité et votre gentillesse. Merci de m’avoir transmis votre rigueur et votre disponibilité, mais aussi de m’avoir appris à être critique, à exploiter une manip jusqu’au bout pour en tirer le maximum d’informations. Merci de m’avoir transmis une partie de vos connaissances et votre savoir-faire. Monsieur le Professeur T. TAHAR Un grand merci pour votre gentillesse et humanité, pour vos précieux conseils et vos encouragements, merci pour vos judicieuses orientations. A mes collègues de CEDOC SVS de la Faculté de Médecine et de Pharmacie de Rabat Je tiens à remercier l’ensemble des personnes qui ont collaboré de près ou de loin à ce travail. 7 Toutes les lettres ne sauraient trouver les mots qu'il faut...? Tous les mots ne sauraient exprimer la gratitude, l'amour, respect, la reconnaissance...? Aussi, c'est tout simplement que...? Je dédie cette thèse ... 8 A MA TRÈS CHÈRE MÈRE Autant de phrases aussi expressives soient-elles ne sauraient montrer le degré d’amour et d’affection que j’éprouve pour toi. A la plus douce et la plus merveilleuse de toutes les mamans. Tu représentes pour moi le symbole de la bonté par excellence. A une personne qui m’a tout donné sans compter. Aucun hommage ne saurait transmettre à sa juste valeur ; l’amour, le dévouement et le respect que je porte pour toi. Sans toi, je ne suis rien, mais grâce à toi j’obtiens mon doctorat national. J’implore Dieu qu’il te procure santé et qu’il m’aide à te compenser tous les malheurs passés. Pour que plus jamais le chagrin ne pénètre ton cœur, car j’aurais encore besoin de ton amour. Je te dédie ce travail qui grâce à toi a pu voir le jour. Je te dédie à mon tour cette thèse qui concrétise ton rêve le plus cher et qui n’est que le fruit de tes conseils et de tes encouragements. Tu n’as pas cessé de me soutenir et de m’encourager, ton amour, ta générosité exemplaire et ta présence constante ont fait de moi ce que je suis aujourd’hui. Tes prières ont été pour moi un grand soutien tout au long de mes études. J’espère que tu trouveras dans ce modeste travail un témoignage de ma gratitude, ma profonde affection et mon profond respect. Puisse Dieu tout puissant te protéger du mal, te procurer longue vie, santé et bonheur afin que je puisse te rendre un minimum de ce que je te dois. Je t’aime maman. 9 A MON TRÈS CHER PÈRE Autant de phrases et d’expressions aussi éloquentes soit-elles ne sauraient exprimer ma gratitude et ma reconnaissance. De tous les pères, tu as été le meilleur, tu as su m’entourer d’attention, m’inculquer les valeurs nobles de la vie, m’apprendre le sens du travail, de l’honnêteté et de la responsabilité. Tes conseils ont toujours guidé mes pas vers la réussite. Ta patience sans fin, ta compréhension et ton encouragement sont pour moi le soutien indispensable que tu as toujours su m’apporter. Je te dois ce que je suis aujourd’hui et ce que je serai demain et je ferai toujours de mon mieux pour rester ta fierté et ne jamais te décevoir. Rien au monde ne vaut les efforts fournis jour et nuit pour mon éducation et mon bien être. Ce travail est le fruit des sacrifices que vous avez consentis pour mon éducation et ma formation. Que Dieu le tout puissant te préserve, t’accorde santé, bonheur, quiétude de l’esprit et te protège de tout mal. 10 A MES CHERS ET ADORABLE FRERES ET SŒUR Abdelaziz, mon deuxième père, Najia la prunelle de mes yeux, Abdelhak, Le doux, au cœur généreux et Simohammed. Vous avez été à mes côtés pendant toutes les étapes de mes études, je vous en suis très reconnaissante. L’encouragement, les conseils et les soutiens que vous m’avez apporté étaient et reste la bouffée d’oxygène qui me ressourçait dans les moments pénibles Quoique je puisse dire et écrire, Aucune dédicace ne peut exprimer la profondeur des sentiments fraternels et d’amour, d’attachement que j’éprouve à votre égard.
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