Polyomaviruses and Human Diseases ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 568 HOT TOPICS IN INFECTION AND IMMUNITY IN CHILDREN II Edited by Andrew J. Pollard and Adam Finn Volume 569 EARLY NUTRITION AND ITS LATER CONSEQUENCES: NEW OPPORTUNITIES Edited by Berthold Koletzko, Peter Dodds, Hans Akerbloom, and Margaret Ashwell Volume 570 GENOME INSTABILITY IN CANCER DEVELOPMENT Edited by Erich A. Nigg Volume 571 ADVANCES IN MYCOLOGY Edited by J.I. Pitts, A.D. Hocking, and U. Thrane Volume 572 RETINAL DEGENERATIVE DISEASES Edited by Joe Hollyfield, Robert Anderson, and Matthew La Vail Volume 573 EARLY LIFE ORIGINS OF HEALTH AND DISEASE Edited by Marelyn Wintour-Coghlan and Julie Owens Volume 574 LIVER AND PANCREATIC DISEASES MANAGEMENT Edited by Nagy A. Habib and Ruben Canelo Volume 575 DIPEPTIDYL AMINOPEPTIDASES: BASIC SCIENCE AND CLINICAL APPLICATIONS Edited by Uwe Lendeckel, Ute Bank, and Dirk Reinhold Volume 576 N-ACETYLASPARTATE: A UNIQUE NEURONAL MOLECULE IN THE CENTRAL NERVOUS SYSTEM Edited by John R. Moffett, Suzannah B. Tieman, Daniel R. Weinberger, Joseph T. Coyle and Aryan M.A. Namboodiri A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. Polyomaviruses and Human Diseases Edited by Nasimul Ahsan, M.D., FACP Mayo Clinic - College of Medicine, Mayo Clinic Transplant Center, Jacksonville, Florida, U.S.A. Springer Science+Business Media Landes Bioscience / Eurekah.com springer Science+Business Media Eurekah.com / Landes Bioscience Copyright ©2006 Eurekah.com and Springer Science+Business Media All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system; for exclusive use by the Purchaser of the work. Printed in the U.S.A. Springer Science+Business Media, 233 Spring Street, New York, New York 10013, U.S.A. Please address all inquiries to the Publishers: Eurekah.com / Landes Bioscience, 810 South Church Street, Georgetown, Texas, U.S.A. 78626 Phone: 512/ 863 7762; FAX: 512/ 863 0081 http ://www .eurekah.com http://www.landesbioscience.com Polyomaviruses and Human Diseases, edited by Nasimul Ahsan, Landes Bioscience / Eurekah.com / Springer Science+Business Media dual imprint / Springer series: Advances in Experimental Medicine and Biology ISBN: 0-387-29233-0 While the authors, editors and publisher believe that drug selection and dosage and the specifications and usage of equipment and devices, as set forth in this book, are in accord with current recommend ations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book. In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefully review and evaluate the information provided herein. Library of Congress Cataloging-in-Publication Data Polyomaviruses and human diseases / edited by Nasimul Ahsan. p.; cm. ~ (Advances in experimental medicine and biology ; v. 577) Includes bibliographical references and index. ISBN 0-387-29233-0 1. Polyomavirus infections. 2. Polyomaviruses. I. Ahsan, Nasimul. II. Series. [DNLM: 1. Polyomavirus Infections. 2. BK Virus. 3. JC Virus. QW165.5P2P783 2006] QR201.P732P65 2006 616.9'l~dc22 2005025594 DEDICATION To the memories of Late Dr. Humayun Kabir who inspired me to study medicine and of Late Dr. Gerald Stoner, whose pioneering works inspired many scientists to study Polyomavirus. To my parents for their everlasting support. To my family: Arzumand (wife), Shaon (daughter), and Naveed (son) for their love and sacrifice. FOREWORD Science never solves apr oblem without creating ten more Geor ge Bernard Shaw How prophetic the above words prove to be when applied to the advances of 20th century medicine. Prior to Banting and Best, chnicians were unaware of the ravages of diabetes, patients simply wasted away and died. Following the purifica tion of insulin, clinicians now had to deal with diabetic retinopathy, diabetic neph ropathy and all the other complications of long-term diabetes. A little over 50 years ago, the first successful human kidney transplant was performed in Boston. The first 30 years of the experience had successes when compared to the alternative but were a constant struggle to get even 50% of the grafts from deceased donors to survive more than a year. However, the science continued to advance knowledge of the immune response. With this came more and increasingly powerful tools for the clinician. Suddenly, success rates of 80-90% at one year were attainable. With this success came new problems, new complications and clinicians now had to worry about the long-term consequences of their therapy as patients were surviving with functional grafts for extended periods. A particular infectious complication evolved with the application of ever more powerful immunosuppressant drugs. Astute clinicians noted that occasionally cellular rejections seemed to get worse with steroids. Despite their best efforts and the use of powerful drugs, patients lost their grafts to overwhelming interstitial infiltrates not seen before. In the mid-1990s, investigators reported series of patients with BK nephropathy due to emergence of polyomavirus reactivation in the kidney. Polyomaviruses had been previously de scribed and had been known to cause disease in immunocompromised hosts. These had included CNS disease due to the JC virus, association of cancer with members of the Polyoma family particularly JC and SV40, and hemorrhagic cystitis. How ever, the newly recognized entity of BK nephropathy began to reach epidemic pro portions with some centers reporting infections in the 15-20% range. This was clearly a complication of powerful immunosuppressive drugs and sparked a renewed inter est in the study of all members of this virus family. This book is a compilation of that research explosion. The contributors have done a great service by compiling in one place the most complete collection of knowledge regarding the polyomaviruses. The clinical aspects of the disease af fecting kidney transplant recipients including detection, diagnosis, monitoring and treatment are laid out for the reader in a rational and readable manner. Polyoma virus interaction with the central nervous system as well as their association with malignancy is covered as well. A compilation of the basic science aspects of this family of viruses is gathered in one place for the first time. This work should serve those interested in these viruses and the diseases caused by them. Under standing all aspects of a disease is the first step in conquering it. Many in the field of transplantation and virology should find this book useful in future endeavors and as with any good text, it should serve as a guide and as an inspiration to those who follow. Thomas A. Gonwa, M.D., FACP PREFACE "Life is short; art is long; opportunity fugitive; experience delusive; judgment difficult. It is the duty of the physician not only to do that which immediately belongs to him, but likewise to secure the cooperation of the sick, of those who are in atten dance, and of all the external agents." Oenopieles Hippocrates What prompted this book was a seeming imbalance, between advancements made in science and what appears to be known generally. We admit that only mod est progress has been made in understanding many infectious diseases such as those caused by polyomavirus. In studying infectious diseases around the world, one ends by regarding them as biological individuals, which have survived centuries, span ning human generations. Polyomavirus lends itself to such treatment because of its life cycles in the animal (human) worlds, the salient facts of which have all been elucidated within the last 30 years. However, the means of diagnosis and treatment of this virus have become, if not perfect, at least somewhat effective, and they de serve as full an explication as possible. Many valuable monographs we possess, and even volumes of admirable papers have been published on this virus, but the former are so scattered as to be out of reach for a great number of interested readers, and the latter so academically de tailed as to be unsuitable except for basic scientists. Why, then, not write a succinct manual of practice, limited to the main theme of clinical care? Ah, but an explosion of information in this field mandates both a far-reaching scope of coverage and in- depth analysis to present the complete and current picture. To meet these objectives, this book has been arranged to contain an ample outline of the history, pathology, symptoms, and treatment of diseases induced by human polyomavirus, without any detail of controversies or conflicting opinions. The use of multiple authors was es sential to ensure the all-inclusive nature of this text. Many of these authors are pio neers in the field, and all have extensive experience studying or treating this vims. Because it is comprehensive, this book has broad applications for a variety of read ers, including medical students, virologists, pathologists, and transplant specialists, as well as patients. The book is divided into four sections covering the entirety of polyomaviruses from basic science considerations to clinical implications. The first section begins with a general discussion of the virus including immunology, epidemiology, and molecular and experimental virology. Due to increasing interests in the diseases caused by Polyoma-BK vims in transplant recipients, an entire second section ex plores transplant-related pathobiology, histopathology, diagnosis, management, and pharmacotherapy. The third section discusses the afflictions and diseases caused by Polyoma-JC virus, particularly that of the central nervous system. The fourth sec tion deals with neoplastic associations of polyomaviruses. From the sketch just given, it is evident that the book has no higher goal than that of a compilation, with the addition of whatever information the distinguished authors may have from some of their own work. A few who read our book may be attracted to study the diseases that are caused by the polyomaviruses. Altogether it is earnestly hoped that the information contained in this book may be found useful, facilitating future research in this field. We wish, as well, to recognize and honor the careers of several friends and colleagues who contributed unstintingly to research in the field of polyomavirus. To that end, the authors and editors have done what they can do, and tried to present the views and experiments of everyone, as best as they could. If any mistakes have occurred, and in a work like the present it is very possible, I shall thankfully receive notification of such errors, and shall take the earliest opportunity to correct them. If any apology be necessary for the publication of the following work, the editor ac cepts responsibility. Our book will be an agent of change and betterment. Even the best books have only a small effect on what people do. If our work benefits patients and draws investigators into our field, we are satisfied. That will be enough. Nasimul Ahsan, M.D., FACP