273 Current Topics in Microbiology and Immunology

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1 273 Current Topics in Microbiology and Immunology Editors R. W. Compans, Atlanta/Georgia M.D. Cooper, Birmingham/Alabama H. Koprowski, Philadelphia/Pennsylvania F. Melchers, Basel. M.B.A. Oldstone, La Jolla/California s. Olsnes, Oslo M. Potter, Bethesda/Maryland P.K. Vogt, La Jolla/California H. Wagner, Munich

2 Springer-Verlag Berlin Heidelberg GmbH

3 w. Doerfler P. Bohm (Eds.) Adenoviruses: Model and Vectors in Virus-Host Interactions Immune System, Oncogenesis, Gene Therapy With 35 Figures and 14 Tables Springer

4 Professor Dr. Walter Doerfler Institut fur Klinische und Molekulare Virologie Universitat Erlangen-Niirnberg Erlangen, Germany Petra Bahm Institut fur Genetik UniversWit zu Kaln Weyertal Kaln, Germany Cover Illustration by Lennart Philipson (this volume): Binding of 3 receptor IgG domains on the outside of the 3 adenovirus fiber knob polypeptides. The complex is viewed down the fiber shaft. ISSN X ISBN ISBN (ebook) DOI / This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Spnnger-Verlag Berlin Heidelberg GmbH. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 2004 Originally published by Springer-Verlag Berlin Heidelberg New York in 2004 Softcover reprint of the hardcover I st edition 2004 Library of Congress Catalog Card Number The use of general descriptive names, registered names, trademarks, 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. Product liability: The publishers cannot guarantee the accuracy for any information about dosage and application contained in this book. In every individual case the user must check such information by consulting other relevant literature. Cover Design: Design & Production GmbH, Heidelberg Typesetting: Stiirtz AG, Wiirzburg Production Editor: Angelique Gcouta, Berlin Printed on acid-free paper SPIN: /

5 Preface Science works at its best when new observations are pursued by the persevering investigator to elucidate the molecular mechanisms behind a discovered phenomenon. Time and again, basic research without any, at the time obvious, immediate medical or biological relevance has proved to be the most rewarding endeavor for the promotion of knowledge in science. Biology, with the undisputable advantage of several billions of years in evolutionary experience, is too far ahead for us to be able to anticipate the next important scientific discovery. As in the past, we will have to rely on hard work, analytical scrutiny, and serendipity to guide us to progress. Narrowly focused research aimed at "solving" important medical problems will rarely be worth the time, money, and effort spent on it. The successful design of the Human Genome Project has been based on 50 years of research in molecular biology on a very wide scope, and hence is a case in point rather than an example to the contrary. In keeping with this long-standing experience, Adenoviruses: Model and Vectors in Virus-Host Interactions presents chapters which are devoted to basic research on a group of viruses which have helped unravel many of the basic mechanisms in mammalian molecular biology. While the chapters in the preceding volume 272 of this series dealt with problems of basic molecular virology, we now turn to studies in which adenoviruses have helped to answer more complex problems in biology: How does the virus attach to and penetrate the cell surface? Which mechanisms can the virus avail itself of to circum-vent the immune defenses of the host? Although tumor biology remains as ephemeral and complex as ever, adenovirus oncogenesis offers a resourceful model with the advantage of a high tumor incidence and a short latency period. Different mechanisms have been examined here to better understand cell transformation. The traditional thought that products of the viral El region and their interactions with host proteins could play a crucial role in eliciting the oncogenic response has been carefully documented and widely exploited. Moreover, tumorigenesis being a highly complicated biological event, a more generally applicable model has been investigated. Foreign DNA insertion into an established mammalian genome alters patterns of DNA methylation and transcription

6 VI Preface in the genome of the host. The ensuing structural and functional perturbations are presumed to contribute to the transformation process. Lastly, much work has been performed adapting adenoviruses as pliable and innocuous gene transfer vectors for human somatic gene therapy. With fatefully bad news from clinical applications of viral gene transfer vectors, we seem to be still very far from this goal. However, basic research on adenovirus vectors and their interactions with host animals, their fate in the living organisms, and the expression of their payload in selected organs, if anything, may improve our knowledge on how to introduce foreign genes into living cells and organisms. Should that aim ever be met, basic research will have led the way. Several of the contributions in this volume point out directions in which solutions to complex biological and medical problems can be sought. Again, it is a pleasure to thank our colleagues for their excellent chapters and Ms. Clauss of Springer-Verlag in Heidelberg for editorial assistance. Erlangen/K6ln, August 2003 Walter Doerfler Petra B6hm

7 List of Contents 1 Immune System Evasion of the Immune System by Adenoviruses G.E. Blair and M.E. Blair-Zajdel Immune Evasion by Adenovirus E3 Proteins: Exploitation of Intracellular Trafficking Pathways M. Windheim, A. Hilgendorf, and H.-G. Burgert The Coxsackie-Adenovirus Receptor-A New Receptor in the Immunoglobulin Family Involved in Cell Adhesion L. Philipson and R.E Pettersson Mechanisms of E3 Modulation of Immune and Inflammatory Responses S.P. Fessler, E Delgado-Lopez, and M.S. Horwitz Oncogenesis Modulation of Oncogenic Transformation by the Human Adenovirus EIA C-Terminal Region G. Chinnadurai Cell Transformation by Human Adenoviruses C. Endter and T. Dobner Tumorigenesis by Adenovirus Type 12 in Newborn Syrian Hamsters U. Hohlweg, A. Dorn, M. Hosel, D. Webb, R. Buettner, and W. Doerfler 215 EIA-Based Determinants of Oncogenicity in Human Adenovirus Groups A and C J.E Wiliams, Y. Zhang, M.A. Williams, S. Hou, D. Kushner, and R.P. Ricciardi

8 VIII List of Contents 3 Gene Therapy Replicating Adenoviruses in Cancer Therapy M. Dobbelstein Adenovirus Vectors: Biology, Design, and Production M.J. Imperiale and S. Kochanek Subject Index

9 List of Contributors (Their addresses can be found at the beginning of their respective chapters.) Blair, G.E. 3 Blair-Zajdel, M.E. 3 Buettner, R. 215 Burgert, H.-G. 29 Chinnadurai, G. 139 Delgado-Lopez, E 113 Dobbelstein, M. 291 Dobner, T. 163 Doerfler, W. 215 Dorn, A. 215 Endter, C. 163 Fessler, S.P. 113 Hilgendorf, A. 29 Hohlweg, U. 215 Horwitz, M.S. 113 Hosel, M. 215 Hou, S. 245 Imperiale, M.J. 335 Kochanek, S. 335 Kushner, D. 245 Pettersson, R.E 87 Philipson, L. 87 Ricciardi, R.P. 245 Webb, D. 215 Williams, J.E 245 Williams, M.A. 245 Windheim, M. 29 Zhang, Y. 245