Characterization of Hepatitis C Virus Interaction with Heparan Sulfate Proteoglycans Yan Xu
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Characterization of Hepatitis C Virus interaction with heparan sulfate proteoglycans Yan Xu To cite this version: Yan Xu. Characterization of Hepatitis C Virus interaction with heparan sulfate proteoglycans. Hu- man health and pathology. Université du Droit et de la Santé - Lille II, 2014. English. NNT : 2014LIL2S021. tel-01201824 HAL Id: tel-01201824 https://tel.archives-ouvertes.fr/tel-01201824 Submitted on 18 Sep 2015 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 DE DOCTORAT DE L’UNIVERSITÉ LILLE II École Doctorale Biologie –Santé de Lille Pour l’obtention du grade de : Docteur de L’UNIVERSITÉ LILLE II Thèse soutenue le 16 Septembre 2014 Caractérisation des interactions du Virus de l'Hépatite C avec les protéoglycanes à héparane sulfate Characterization of Hepatitis C Virus interaction with heparan sulfate proteoglycans Centre d’Infection & d’Immunité de Lille (CIIL), Inserm U1019, CNRS UMR 8204, Institut Pasteur de Lille, Équipe Virologie Moléculaire & Cellulaire de l’Hépatite C !"#$%&$'#()$(*+,-$.((Dr Jean Dubuisson! ( ! /#0-$1&0$($&(-2'&$1'$(3'45"6'$7$1&(38#.( ( Yan XU Membres du Jury: Président Pr. Didier HOBER Rapporteur Pr. Sandrine CASTELAIN Rapporteur Pr. Philip MEULEMAN Examinateur Dr. Sandrine BELOUZARD Examinateur Dr. François HELLE Directeur de thèse Dr. Jean DUBUISSON 1 To my parents and my dearest friend Manuel 2 Dreams Hold fast to dreams For if dreams die Life is a broken-winged bird That cannot fly. Hold fast to dreams For when dreams go Life is a barren field Frozen with snow. -Langston Hughes 3 ACKNOWLEDGMENTS At the beginning, I would like to thank all the members of jury: professors Didier Hober, Philip Meuleman and Sandrine Castelain, and doctors François Helle and Sandrine Belouzard, and my supervisor Dr. Jean Dubuisson. Thanks to all of you for the attendance and participation in my thesis defence. Then, I would like to give my sincere gratitude again to my supervisor Dr. Jean Dubuisson. Thanks for your initial help and the precious opportunity given to me so that I could do my PhD study in your laboratory. Thanks very much for your patience and great kindness to me all along the way. Also, thanks for your scientific guidance and putting in. Next, I would like to sincerely acknowledge my “petit chef ” Dr. Sandrine Belouzard. Thanks for your generous access to me in the whole process of my project. With you, I learned a lot, from basic experimental techinque to critical thinking on the results. I believe that your strict attitude and whole-hearted dedication into scientific research, as well as your confident decision-making manner have already infected me, and from which I can benefit for my future career. Hereafter, I also thank other scientists including Drs Guangxiang Luo, Mansun Law, Steven Foung and Jane A. McKeating, for your kindly providing us the antibodies that are very important for this work. And then thanks to Dr. Karin Séron, for your technical assistance which contributed a lot to this work. Certainly, thanks very much for the scientific input from our collaborators Dr. Allain Fabrice and Pierre Martinez. I am very grateful to M. Sophana Ung. Thanks for your scientific and plenty of non-scientific support. Also, for all our talking and telling me “this world is not black and white”. Another impressing meet- Pr. Yves Rouillé. You are so wise and farsighted. Your passion to research is obvious. You are always in the state of thinking. Very nice to meet you and talk with you, and also thank you for your professional contribution to our work. Then, many thanks to people in the lab. including Laurence, Muriel, Anne, Rayan, Juliette, Allison, Marie-Emmanuelle, Nathalie, Claire, Adeline, Lucie, Nana, Lison, Laura, and a pair of old mates: Czes and André. Also thanks to previous members : Sohail, Ahmed, Julie, PYD, Noémie and Thibaut. And, to my French teacher Anaïs who makes me like French Language more and more. In a word, thanks to all the people ‘‘J'ai rencontré d’ici’’, thanks for your help and those time we passed together. At last, I want to thank friends here Fan, Jia, Odile and Julie. Thanks for your help, and the time with you that enriched my days in France. Also, thanks to my foundation support from CSC and my family backing, which together made my short ‘‘life journey’’ in France possible, then I could travel around Europe a bit, know China better and love her more. 4 RÉSUMÉ .................................................................................................................................................................. 7 RÉSUMÉ LONG ...................................................................................................................................................... 9 ABSTRACT............................................................................................................................................................22 LIST OF ILLUSTRATIONS.................................................................................................................................24 LIST OF TABLES .................................................................................................................................................25 ABBREVIATIONS................................................................................................................................................26 INTRODUCTION .................................................................................................................................................29 I. GENERAL INTRODUCTION OF VIRAL HEPATITIS C ............................................................................29 1. HEPATITIS C EPIDEMIOLOGY ...........................................................................................................................................29 2. NATURAL HISTORY OF HCV INFECTION ........................................................................................................................31 3. DIAGNOSIS AND TREATMENT OF HCV INFECTION......................................................................................................32 4. MOLECULAR BIOLOGY OF HCV........................................................................................................................................36 4.1 HCV classification and genotype distribution ................................................................................................36 4.2 HCV genome and viral proteins............................................................................................................................37 4.3 The HCV life cycle........................................................................................................................................................43 4.4 HCV particles.................................................................................................................................................................47 4.5 HCV model system.......................................................................................................................................................52 II. HCV VIRAL PARTICLE COMPONENTS IN VIRAL ENTRY ...................................................................61 1. HCV HOST CELL TROPISM AND TRANSMISSION ROUTES ............................................................................................61 2. HCV ENTRY INTO HEPATOCYTES ....................................................................................................................................63 3. HCV ENVELOPE GLYCOPROTEINS IN VIRAL ENTRY......................................................................................................67 4. HYPERVARIABLE REGION 1 OF ENVELOPE GLYCOPROTEIN E2 .................................................................................70 5. HCV PARTICLE COMPONENT APOE ................................................................................................................................71 5.1 ApoE protein and its isoforms in lipid metabolism and in AD.................................................................72 5.2 ApoE in infectious diseases .....................................................................................................................................77 5.3 Influence of apoE isoforms in the HCV life cycle............................................................................................82 6. OTHER APOLIPOPROTEINS ...............................................................................................................................................84 6.1 ApoCs in lipoprotein metabolism and HCV infection ..................................................................................84 6.2 ApoAI in lipoprotein metabolism and in HCV infection .............................................................................87 III. CELLULAR FACTORS IN HCV ENTRY .....................................................................................................89 1. HCV ATTACHMENT FACTORS ..........................................................................................................................................89