Table Of ContentDNA Tumor Viruses
Oncogenic Mechanisms
Edited by
Giuseppe Barbanti-Brodano
University of Ferrara
Ferrara, Italy
Mauro Bendinelli
University of Pisa
Pisa, Italy
and
Herman Friedman
University of South Florida
Tampa, Florida
Springer Science+Business Media, LLC
Library of Congress Cataloging-in-Publication Data
DNA tumor viruses . ancogenic mechanisms / edited by Giuseppe Barbanti
-Brodano, Maure Bendlne 111, Herman Friedman.
p. cm. — (Infectious agents and pathogenesis)
Includes bibliographical references and index.
ISBN 978-1-4899-1102-5
1. Oncogenic viruses. I. Barbant1-Brodano, Giuseppe.
II. Bendinelli, Mauro. III. Friedman, Herman, 1931-
IV. Series.
[DNLM: 1. DNA Tumor Viruses—pathogenicity. 2. TumorVirus
Infections—complications. 3. Neoplasms—etiology. 4. Cell
Transformation, Neoplastic. 5. Viral Vaccines. QW 166D6289 1995]
QR372.06D595 1995
616.99'4071--dc20
DNLM/DLC
for Library of Congress 95-42518
CIP
ISBN 978-1-4899-1102-5 ISBN 978-1-4899-1100-1 (eBook)
DOI 10.1007/978-1-4899-1100-1
© Springer Science+Business Media New York 1995
Originally published by Plenum Press, New York in 1995
Softcover reprint of the hardcover 1st edition 1995
10 98765432 1
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any
form or by any means, electronic, mechanical, photocopying, microfilming, recording, or
otherwise, without written permission from the Publisher
DNA Tumor Viruses
Oncogenic Mechanisms
INFECTIOUS AGENTS AND PATHOGENESIS
Series Editors: Mauro Bendinelli, University of Pisa
Herman Friedman, University of South Florida
COXSACKIEVIRUSES
A General Update
Edited by Mauro Bendinelli and Herman Friedman
DNA TUMOR VIRUSES
Oncogenic Mechanisms
Edited by Giuseppe Barbanti-Brodano, Mauro Bendinelli, and
Herman Friedman
FUNGAL INFECTIONS AND IMMUNE RESPONSES
Edited by Juneann W. Murphy, Herman Friedman, and
Mauro Bendinelli
MYCOBACTERIUM TUBERCULOSIS
Interactions with the Immune System
Edited by Mauro Bendinelli and Herman Friedman
NEUROPATHOGENIC VIRUSES AND IMMUNITY
Edited by Steven Specter, Mauro Bendinelli, and
Herman Friedman
PSEUDOMONAS AERUGINOSA AS AN OPPORTUNISTIC PATHOGEN
Edited by Mario Campa, Mauro Bendinelli, and
Herman Friedman
PULMONARY INFECTIONS AND IMMUNITY
Edited by Herman Chmel, Mauro Bendinelli, and
Herman Friedman
VIRUS-INDUCED IMMUNOSUPPRESSION
Edited by Steven Specter, Mauro Bendinelli, and
Herman Friedman
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.
Contributors
LAURE AURELIAN • Virology/Immunology Laboratories, Department of Phar
macology and Experimental Therapeutics, University of Maryland School of
Medicine, Baltimore, Maryland 21201-1192; and Departments of Biochemistry
and Comparative Medicine, The Johns Hopkins Medical Institutions, Bal
timore, Maryland 21205
GIUSEPPE BARBANTI-BRODANO • Institute of Microbiology, School ofMedi
cine, University of Ferrara, 1-44100 Ferrara, Italy
MAURO BOIOCCHI • Division of Experimental Oncology 1, Centro di Riferi
mento Oncologico, 33081 Aviano (PN), Italy
MARIE ANNICK BUENDIA • Unite de Recombinaison et Expression Gene
tique, INSERM U163, Departement des Retrovirus, Institut Pasteur, 75724
Paris Cedex 15, France
M. SAVERIA CAMPO • The Beatson Institute for Cancer Research, CRC Beat
son Laboratories, Bearsden, Glasgow G61 IBD, Scotland
ANTONINO CARBONE • Division of Pathology, Centro di Riferimento Onco
logico, 33081 Aviano (PN), Italy
MICHELE CARBONE • Department of Pathology, University of Chicago, Chi
cago, Illinois 60637
E. CASELLI • Institute of Microbiology, University of Ferrara, 1-44100 Ferrara,
Italy
E. CASSAI • Institute of Microbiology, University of Ferrara, 1-44100 Ferrara,
Italy
CHRISTA CERNI • Institute of Tumor Biology-Cancer Research, University of
Vienna, 1090 Vienna, Austria
DOROTHY H. CRAWFORD • Department of Clinical Sciences, London
School of Hygiene and Tropical Medicine, London WCIE 7HT, England
LIONEL CRAWFORD • ICRF Tumour Virus Group, Department of Pathology,
University of Cambridge, Cambridge CB2 lQP, England
VALLI DE RE • Division of Experimental Oncology 1, Centro di Riferimento
Oncologico, 33081 Aviano (PN), Italy
v
vi CONTRIBUTORS
DARIO DI LUCA • Institute of Microbiology, University of Ferrara, 1-44100
Ferrara, Italy
JOSEPH A. DiPAOLO • National Cancer Institute, Laboratory of Biology, Be
thesda, Maryland 20892
RICCARDO DOLCETII • Division of Experimental Oncology 1, Centro di
Riferimento Oncologico, 33081 Aviano (PN), Italy
M. EICKMANN • Institut fur Virologie, Philipps-Universitat, D-35037 Marburg,
Germany
JEAN FEUNTEUN • Institut Gustave Roussy, Laboratoire d'Oncologie Mo
leculaire, 94805 Villejuif, France
ANNUNZIATA GLOGHINI • Division of Pathology, Centro di Riferimento On
cologico, 33081 Aviano (PN), Italy
MARIA E. JACKSON • The Beatson Institute for Cancer Research, CRC Beatson
Laboratories, Bearsden, Glasgow G61 lBD, Scotland
LAYLA KARIMI • Department of Clinical Sciences, London School of Hygiene
and Tropical Medicine, London WCIE 7HT, England
H. KERN • Institut fUr Zellbiologie, Philipps-Universitat, D-35037 Marburg,
Germany
LAURA de LELLIS • Institute of Microbiology, School of Medicine, University
of Ferrara, 1-44100 Ferrara, Italy
PETER G. MEDVECZKY • Department of Medical Microbiology and Immunol
ogy, University of South Florida, Tampa, Florida 33612-4799
T. MOCKENHAUPT • Institut fur Virologie, Philipps-Universitat, D-35037 Mar
burg, Germany
PAOLO MONINI • Institute of Microbiology, School of Medicine, University of
Ferrara, 1-44100 Ferrara, Italy
ANDREW J. MORGAN • Department of Pathology and Microbiology, School of
Medical Sciences, University of Bristol, Bristol BS8 lTD, England
MElHAN NONOYAMAt • Tampa Bay Research Institute, St. Petersburg, Flor
ida 33716
JOSEPH S. PAGANO • Departments of Microbiology and Immunology and
Medicine, UNC Lineberger Comprehensive Cancer Center, University of
North Carolina, School of Medicine, Chapel Hill, North Carolina 27599-7295
HARVEY I. PASS • Thoracic Oncology Section, National Cancer Institute, Na
tional Institutes of Health, Bethesda, Maryland 20892
PASCAL PINEAU • Unite de Recombinaison et Expression Genetique, INSERM
U163, Departement des Retrovirus, Institut Pasteur, 75724 Paris Cedex 15,
France
K. RADSAK • Institut fur Virologie, Philipps-Universitat, D-35037 Marburg, Ger
many
F. ANDREW RAY • Life Sciences Division, Los Alamos National Laboratory, Los
Alamos, New Mexico 87545; present address: Department of Microbiology, Im
munology and Molecular Genetics, The Albany Medical College, Albany, New
York 12208-3479
tDeceased.
CONTRIBUTORS vii
B. REIS • Institut fur Virologie, Philipps-Universitiit, D-35037 Marburg, Ger
many
M. RESCHKE • Institut fUr Virologie, Philipps-Universitiit, D-35037 Marburg,
Germany
ROBERT P. RICCIARDI • Department of Microbiology, School of Dental Medi
cine, and Graduate Program in Microbiology and Virology, University of Penn
sylvania, Philadelphia, Pennsylvania 19104
PAOlA RIZZO • Department of Pathology, University of Chicago, Chicago,
Illinois 60637
SIEGFRIED SCHERNECK • Max-Delbruck-Centrum for Molecular Medicine,
Tumorgenetics, 13122 Berlin, Germany
CHRISTIAN SEELOS • Institute of Tumor Biology-Cancer Research, Univer
sity of Vienna, 1090 Vienna, Austria
DANIEL T. SIMMONS • Department of Biology, University of Delaware, New
ark, Delaware, 19716
NANCY S. SUNG • Departments of Microbiology and Immunology and Medi
cine, UNC Lineberger Comprehensive Cancer Center, University of North
Carolina, School of Medicine, Chapel Hill, North Carolina 27599-7295
AKIKO TANAKA • Tampa Bay Research Institute, St. Petersburg, Florida 33716
CRAIG D. WOODWORTH • National Cancer Institute, Laboratory of Biology,
Bethesda, Maryland 20892
Preface to the Series
The mechanisms of disease production by infectious agents are presently the focus
of an unprecedented flowering of studies. The field has undoubtedly received
impetus from the considerable advances recently made in the understanding of the
structure, biochemistry, and biology of viruses, bacteria, fungi, and other parasites.
Another contributing factor is our improved knowledge of immune responses and
other adaptive or constitutive mechanisms by which hosts react to infection. Fur
thermore, recombinant DNA technology, monoclonal antibodies, and other newer
methodologies have provided the technical tools for examining questions previ
ously considered too complex to be successfully tackled. The most important
incentive of all is probably the regenerated idea that infection might be the
initiating event in many clinical entities presently classified as idiopathic or of
uncertain origin.
Infectious pathogenesis research holds great promise. As more information is
uncovered, it is becoming increasingly apparent that our present knowledge of the
pathogenic potential of infectious agents is often limited to the most noticeable
effects, which sometimes represent only the tip of the iceberg. For example, it is now
well appreciated that pathologic processes caused by infectious agents may emerge
clinically after an incubation of decades and may result from genetic, immunologic,
and other indirect routes more than from the infecting agent in itself. Thus, there is
a general expectation that continued investigation will lead to the isolation of new
agents of infection, the identification of hitherto unsuspected etiologic correla
tions, and, eventually, more effective approaches to prevention and therapy.
Studies on the mechanisms of disease caused by infectious agents demand a
breadth of understanding across many specialized areas, as well as much coopera
tion between clinicians and experimentalists. The series Infectious Agents and Patho
genesis is intended not only to document the state of the art in this fascinating and
challenging field but also to help lay bridges among diverse areas and people.
Mauro Bendinelli
Herman Friedman
ix
Preface
DNA tumor viruses have long been useful experimental models of carcinogenesis
and have elucidated several important mechanisms of cell transformation. Re
search in recent years has shown that human tumors have a multifactorial nature
and that some DNA tumor viruses may playa key role in their etiology. The aim of
this book is to assess our knowledge of DNA tumor viruses by reviewing animal
models, mechanisms of transformation, association with human tumors, and possi
bilities of prevention and control by vaccination.
Animal models of tumor virology have contributed significantly to our under
standing of the epidemiology and pathogenesis of virus-induced tumors. Bovine
papillomaviruses induce papillomas in the intestine of cattle. The papillomas
undergo a transition to carcinomas in cows feeding on bracken fern, which pro
duces a toxin with radiomimetic and immunosuppressive functions. This example
of cooperation between a virus and chemical carcinogens parallels the cooperative
role of human papillomaviruses (HPVs) and herpes simplex virus type 2 (HSV-2)
with environmental carcinogens in the pathogenesis of cervical cancer. Likewise,
hepatocarcinomas appearing in woodchucks chronically infected by woodchuck
hepatitis virus (WIN) provide strong support for the relationship between hepatitis
B virus (HBV) infection and human hepatocellular carcinoma. Also, the fact that
WIN DNA integrates closely to cellular oncogenes suggests a possible molecular
mechanism for the tumorigenesis induced by HBV. Two animal herpesviruses
inducing Iymphoproliferative diseases, Marek's disease virus and Herpesvirus saimiri,
are presented as models of lymphomas associated with the human herpesviruses,
Epstein-Barr virus (EBV) , and human herpesvirus 6. Of particular interest is that
the SeOL gene of Herpesvirus saimiri behaves as a viral oncogene like the LMP-l
gene of EBV.
Several chapters discuss the molecular mechanisms of transformation by DNA
tumor viruses. Some important results have been contributed recently in this field.
It was discovered that simian virus 40 (SV40) T antigen, a DNA-binding protein with
pleiotropic functions, induces extensive and severe chromosomal lesions before
the appearance of the transformed phenotype, suggesting that genomic damage is
xi
