Human Cancer Viruses Translational Research in Biomedicine Vol. 1 Series Editor Samuel H.H. Chan Kaohsiung Associate Editor Julie Y.H. Chan Kaohsiung Human Cancer Viruses Principles of Transformation and Pathogenesis Volume Editors John Nicholas Baltimore, Md. Kuan-Teh Jeang Bethesda, Md. T.-C. Wu Baltimore, Md. 35 figures, 9 in color, and 9 tables, 2008 Basel · Freiburg · Paris · London · New York · Bangalore · Bangkok · Shanghai · Singapore · Tokyo · Sydney Translational Research in Biomedicine John Nicholas, PhD Kuan-Teh Jeang, MD, PhD Viral Oncology Program Laboratory of Molecular Microbiology Sidney Kimmel Comprehensive Cancer Center National Institute of Allergy and Johns Hopkins University Infectious Diseases Baltimore, MD 21287 (USA) National Institute of Health Bethesda, MD 20892 (USA) T.-C. Wu, MD, PhD Department of Pathology Johns Hopkins School of Medicine Cancer Research Building II, Room 309 Baltimore, MD 21231 (USA) Library of Congress Cataloging-in-Publication Data Human cancer viruses : principles of transformation and pathogenesis / volume editors, John Nicholas, Kuan-Teh Jeang, T.-C. Wu. p. ; cm. – (Translational research in biomedicine, ISSN 1662-405X ; v.1) Includes bibliographical references and indexes. ISBN 978-3-8055-8576-7 (hard cover : alk. paper) 1. Viral carcinogenesis. 2. Oncogenic viruses. 3. Viral cell transformation. I. Nicholas, John, 1962– II. Jeang, Kuan-Teh. III. Wu, T.-C. IV. Series. [DNLM: 1. Oncogenic Viruses. 2. Tumor Virus Infections. QW 166 H9172 2008] RC268.57.H86 2008 616.99⬘4071–dc22 2008019369 Disclaimer. The statements, options and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. © Copyright 2008 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISSN 1662–405X ISBN 978–3–8055–8576–7 Contents VII Foreword Chan, S.H.H. (Kaohsiung) IX Preface Nicholas, J. (Baltimore, Md.); Jeang, K.-T. (Bethesda, Md.); Wu, T.-C. (Baltimore, Md.) 1 Molecular Epidemiology of Human Papillomavirus Infection Gillison, M.L. (Baltimore, Md.) 20 Molecular Pathogenesis of the Human Papillomavirus: Cervical Cancer as a Model Mao, C.-P.; Wu, T.-C. (Baltimore, Md.) 37 Human Papillomavirus Vaccines Roden, R.; Hung, C.-F.; Monie, A.; Wu, T.-C. (Baltimore, Md.) 63 Hepatitis C Virus Genetics and the Discovery of Mechanism- Based Inhibitors of the NS3/4A Protease and NS5B Polymerase LaFemina, R.L. (Schwenksville, Pa.) 94 Role of the Hepatitis B Virus in Hepatocellular Carcinoma Toh, S.-T.; Lee, C.G. (Singapore) 108 Carcinogenesis Induced by Hepatitis B Virus Cougot, D.; Buendia, M.-A.; Neuveut, C. (Paris) 137 Disease and Pathogenesis Associated with Epstein-Barr Virus Ambinder, R.F. (Baltimore, Md.) 150 The Biology and Molecular Biology Underlying Epstein-Barr Virus Oncogenesis Martin, H.J.; Hayward, S.D. (Baltimore, Md.) 170 Kaposi-Sarcoma-Associated Herpesvirus Clinical Diseases and Viral Pathogenesis Damania, B.; Dittmer, D.P. (Chapel Hill, N.C.) 186 Molecular Biology of Human Herpesvirus 8 Neoplasia Chaudhary, P.M. (Pittsburgh, Pa.); Nicholas, J. (Baltimore, Md.) 211 Human T Cell Leukemia Virus Type 1 and 2: Mechanisms of Pathogenesis Arnold, J.; Green, P.L. (Columbus, Ohio) 228 Chromosomal Instability and Human T Cell Leukemia Virus 1 Transformation Chi, Y.-H.; Jeang, K.-T. (Bethesda, Md.) 239 Author Index 240 Subject Index VI Contents Foreword Welcome to Translational Research in Biomedicine, a new book series dedicated to the dissemination of seminal information in contemporary biomedicine with a translational orientation. Translational research (TR) is now a household word in the arena of contemporary biomedical research, although a universal definition for this term is currently want- ing. In a more restricted sense, TR is often associated with research and development based on the classical bench to bedside approach. Thus, it has been said that ‘the goal of TR is to implement in vivo measurements and leverage preclinical models that more accurately predict drug effects in humans’ [1]; or ‘TR describes a uni-direc- tional effort to test in humans novel therapeutic strategies developed through experi- mentation’ [2]. The current enthusiasm for the application of genomic or stem cell research to therapeutic strategies is also grounded on a similar premise. In a broader sense, TR is taken as a bench to bedside and back approach to foster communication between the scientific community and clinical practitioners [1]. It is a concept that needs the attention from everyone and should be the foundation of a modern under- standing of health provision [3]. If we subscribe to the philosophical connotation that medical research is for the bet- terment of humankind, then we should realize that there is no real demarcation between clinical (bedside) and preclinical (bench) research. This is because the only dif- ference is that human subjects instead of animals, tissues or cells are employed in the studies. Nonetheless, governed by the same ethical principles and guidelines, all of them will reveal information in some aspects of biomedicine. Thus, this monograph series shall take a holistic view on TR that transcends the boundaries between bench and bed- side research. Each volume shall be a synthesis of ideas, technologies and research out- comes that are associated with a particular theme in contemporary biomedicine, to be edited by experts in that field. Some chapters may be up-to-date reviews on fundamental principles that underlie this theme, to be followed by their clinical applications. Other chapters may begin with clinical observations on this theme, to be followed by their underlying cellular and molecular mechanisms. The word ‘translation’ is most com- monly defined as expression of words in another language. Its definitions can be extended to encompass expression in simpler language and uncomplicated interpreta- tion. In this spirit, all volumes in this series will be presented in a fashion that is amenable to nonexperts, be they scientists or clinical practitioners. My sincere thanks go to Drs. John Nicholas, Kuan-Teh Jeang and T.-C. Wu, Editors for this inaugural volume, for their unfailing efforts to make this series a reality. I am particularly in debt to Dr. Jeang for his timely advice during the planning stage of this project. I also wish to acknowledge the capable hands of Rolf Steinebrunner, Stefan Goldbach and Esther Bernhard at S. Karger AG during the development and produc- tion of this series. Last but not least, the publication of Translational Research in Biomedicine would not have been possible without the foresight, enthusiasm and whole-hearted support of my dear friend, Dr. Thomas Karger. Samuel H.H. Chan Series Editor 1 Hörig H, Pullman W: From bench to clinic and 3 Sonntag KC: Implementations of translational medi- back: perspective on the 1st IQPC Translational cine. J Transl Med 2005;3:33–35. Research Conference. J Transl Med 2004;2:44–51. 2 Mankoff SP, Brander B, Ferrone S, Marincola FM: Lost in translation: obstacles to translational medi- cine. J Transl Med 2004;2:14–18. VIII Foreword Preface The genesis of this book stems from a long-standing collaboration between many of its authors in the teaching of viral oncology to postgraduate students at the Johns Hopkins School of Medicine. Recognizing that a number of these students had little or no exposure to the history, landmark contributions or current research in this important and exciting field was the prime motivation for teaching the course and, subsequently, for compiling this book. Studies of human and nonhuman oncogenic viruses have made enormous contributions to our understanding of crucially impor- tant aspects of cell biology and transformation. For many of us who have lived through pivotal advances in viral oncology over the past 4 decades, there is a strong desire, perhaps a feeling of obligation, to share the past and present excitement of the field with a new generation of scientists. This, along with the wish to present a review of human viral oncology as a cohesive topic, represents the mission of this book. The first identification of a tumor-causing virus, Rous sarcoma virus, occurred almost 100 years ago, but it was not until the 1970s that the genetic basis for oncoge- nesis by this and other acutely transforming retroviruses of avian and rodent species was appreciated. Numerous viral oncogenes and their corresponding cellular proto- oncogene counterparts were identified in rapid succession from these altered and defective viruses. These studies launched a new era of research forging insight into the basic mechanisms of cell cycle control and the functions of key genes involved in its regulation. Later studies of DNA tumor viruses simian virus 40 and human aden- ovirus, found to be transforming in culture and animal models, provided the next advances in our understanding of viral oncogenesis and virus manipulation of the cell cycle and cell survival. These viruses served as crucially important models for the study of oncogenesis, linking processes normally utilized by viruses for replication to mechanisms of oncogenesis occurring under conditions nonpermissive to productive replication. The importance of these discoveries to the elucidation of normal cellular