Current Topics in Microbiology and Immunology Christian Münz E ditor Epstein Barr Virus Volume 1 One Herpes Virus: Many Diseases Current Topics in Microbiology and Immunology Volume 390 Series editors Rafi Ahmed School of Medicine, Rollins Research Center, Emory University, Room G211, 1510 Clifton Road, Atlanta, GA 30322, USA Klaus Aktories Medizinische Fakultät, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abt. I, Albert-Ludwigs-Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany Richard W. Compans Department of Microbiology and Immunology, Emory University, 1518 Clifton Road, CNR 5005, Atlanta, GA 30322, USA Max D. Cooper Department of Pathology and Laboratory Medicine, Georgia Research Alliance, Emory University, 1462 Clifton Road, Atlanta, GA 30322, USA Jorge E. Galan Boyer Ctr. for Molecular Medicine, School of Medicine, Yale University, 295 Congress Avenue, room 343, New Haven, CT 06536-0812, USA Tasuku Honjo Faculty of Medicine, Department of Medical Chemistry, Kyoto University, Sakyo-ku, Yoshida, Kyoto 606-8501, Japan Yoshihiro Kawaoka Influenza Research Institute, University of Wisconsin-Madison, 575 Science Drive, Madison, WI 53711, USA Bernard Malissen Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, 13288, Marseille Cedex 9, France Michael B.A. Oldstone Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA Rino Rappuoli Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy Peter K. Vogt Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC-239, La Jolla, CA 92037, USA Honorary Editor: Hilary Koprowski (deceased) Formerly at Biotechnology Foundation, Inc., Ardmore, PA, USA More information about this series at http://www.springer.com/series/82 Christian Münz Editor Epstein Barr Virus Volume 1 One Herpes Virus: Many Diseases Responsible Series Editor: Peter K. Vogt 1 3 Editor Christian Münz Institute of Experimental Immunology University of Zürich Zürich Switzerland ISSN 0070-217X ISSN 2196-9965 (electronic) Current Topics in Microbiology and Immunology ISBN 978-3-319-22821-1 ISBN 978-3-319-22822-8 (eBook) DOI 10.1007/978-3-319-22822-8 Library of Congress Control Number: 2015948721 Springer Cham Heidelberg New York Dordrecht London © Springer International Publishing Switzerland 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Preface We celebrated the 50th anniversary of the discovery of Epstein Barr virus (EBV) in Burkitt’s lymphoma last year. During these 50 years of research on EBV, this first human candidate tumor virus has been found associated with many more malignant diseases in addition to Burkitt’s lymphoma, including Hodgkin’s lym- phoma, nasopharyngeal carcinoma, a subset of gastric carcinomas, rare T/NK cell lymphomas, and many more. However, not only malignant diseases, but also some autoimmune diseases and the lymphocytosis of infectious mononucleosis have been found to be linked to EBV. In addition, we have learned to appreciate that continuous cell-mediated immune control prevents these EBV associated diseases, but cannot inhibit persistent infection, which the virus establishes in more than 90 % of the human adult population. Thus, EBV serves both as a paradigm for viral oncogenesis in humans and life-long immune control of chronic infection at the same time. The changes in the viral host cell and the host’s immune control that determine the switch between these two states, continue to fascinate us and new experimental developments allow us to address this question in much more detail. Our ability to sequence EBV genomes faster and at lower cost allows us to explore the genetic diversity of EBV and its possible disease association for the first time. The recombinant EBV system allows us to generate mutant viruses to address the functional relevance of this diversity and new in vivo models of EBV infection, tumorigenesis, and immune control provide valuable insights into the pathologic relevance of the EBV characteristics that we have mapped during the last 50 years. With these tools in hand we should be able to unravel many more secrets that this human tumor virus keeps and develop vaccines against some of the EBV associated diseases in the next 50 years. This exciting journey is summarized in the two book volumes in front of you. It starts with personal accounts of the discovery, tumor association, and immune control by pioneers of EBV research (Anthony Epstein, George Klein, Vivianna Lutzky, and Dennis Moss). It then continues with the knowledge on EBV genet- ics and epigenetics that has been gained (Paul Farrell, Paul Lieberman, Wolfgang Hammerschmidt, Regina Feederle, Olaf Klinke, Anton Kuthikin, Remy Poirey, Ming-Han Tsai, and Henri-Jacques Delecluse). An overview of EBV associated v vi Preface diseases ranging from infectious mononucleosis and primary immune deficiencies to EBV associated tumors and autoimmune diseases completes the first volume (David Thorley-Lawson, Kristin Hogquist, Samantha Dunmire, Henri Balfour, Jeffrey Cohen, Ann Moormann, Rosemary Rochford, Paul Murray, Andrew Bell, Jane Healy, Sandeep Dave, Nancy Raab-Traub, Kassandra Munger, and Alberto Ascherio). In the second volume individual latent EBV gene products are then dis- cussed (Lori Frappier, Bettina Kempkes, Paul Ling, Martin Allday, Quentin Bazot, Robert White, Arnd Kieser, Kai Sterz, Osman Cen, Richard Longnecker, Rebecca Skalsky, and Bryan Cullen). Viral entry and exit complete the virology chap- ters (Lindsey Hutt-Fletcher, Luidmila Chesnokova, Ru Jiang, Jessica McKenzie, and Ayman El-Guindy). The remainder of volume two is dedicated to the EBV specific immune response (Martin Rowe, Anna Lünemann, David Nadal, Jaap Middeldorp, Andrew Hislop, Graham Taylor, Maaike Ressing, Michiel van Gent, Anna M. Gram, Marjolein Hooykaas, Sytse Piersma, and Emmanuel Wiertz), in vivo models of EBV infection (Fred Wang, Janine Mühe, and Christian Münz), and EBV specific therapies (Stephen Gottschalk, Cliona Rooney, Corey Smith, Rajiv Khanna, Jennifer Kanakry, and Richard Ambinder). The resulting picture of 32 chapters on EBV biology will hopefully inspire many more young scientists to join research on this paradigmatic human tumor virus. Indeed we might just have now the toolbox in hand not only to transfer discove- ries in preclinical infection models to EBV, but also use EBV itself as a human model pathogen to learn more about the human immune system, viral dynamics in the human population, and the intricacies of EBV infection. Zürich, Switzerland Christian Münz Contents Part I History Why and How Epstein-Barr Virus Was Discovered 50 Years Ago ....... 3 Anthony Epstein Tumor Associations of EBV—Historical Perspectives ................. 17 George Klein EBV-Specific Immune Response: Early Research and Personal Reminiscences ..................................... 23 D.J. Moss and V.P. Lutzky Part II Virus Genetics and Epigenetics Epstein–Barr Virus Strain Variation ............................... 45 Paul J. Farrell Chromatin Structure of Epstein–Barr Virus Latent Episomes ......... 71 Paul M. Lieberman The Epigenetic Life Cycle of Epstein–Barr Virus .................... 103 Wolfgang Hammerschmidt Epstein–Barr Virus: From the Detection of Sequence Polymorphisms to the Recognition of Viral Types .................................. 119 Regina Feederle, Olaf Klinke, Anton Kutikhin, Remy Poirey, Ming-Han Tsai and Henri-Jacques Delecluse vii viii Contents Part III Viral Infection and Associated Diseases EBV Persistence—Introducing the Virus ........................... 151 David A. Thorley-Lawson Infectious Mononucleosis ........................................ 211 Samantha K. Dunmire, Kristin A. Hogquist and Henry H. Balfour Primary Immunodeficiencies Associated with EBV Disease ............ 241 Jeffrey I. Cohen Burkitt’s Lymphoma ............................................ 267 Rosemary Rochford and Ann M. Moormann Contribution of the Epstein-Barr Virus to the Pathogenesis of Hodgkin Lymphoma .......................................... 287 Paul Murray and Andrew Bell The Role of EBV in the Pathogenesis of Diffuse Large B Cell Lymphoma .............................................. 315 Jane A. Healy and Sandeep S. Dave Nasopharyngeal Carcinoma: An Evolving Role for the Epstein–Barr Virus ....................................... 339 Nancy Raab-Traub EBV and Autoimmunity ......................................... 365 Alberto Ascherio and Kassandra L. Munger Index ......................................................... 387 Part I History