Table Of ContentCONTEMPORARY TOPICS
IN IMMUNOBIOLOGY
6
VOLUME
CONTEMPORARY TOPICS IN IMMUNOBIOLOGY
General Editor
M. G. Hanna, Jr.
Frederick Cancer Research Center
Frederick, Maryland
Editorial Board:
Max D. Cooper
University of Alabama
Birmingham, Alabama
A. J. S. Davies
Chester Beatty Research Institute
London, England
John J. Marchalonis
Frederick Cancer Research Center
Frederick, Maryland
Victor Nussenzweig
New York University School of Medicine
New York, New York
George W. Santos
Johns Hopkins University
Baltimore, Maryland
Osias Stutman
Sloan-Kettering Institute for Cancer Research
New York, New York
Noel L. Warner
The Walter and Eliza Hall Institute
Victoria, Australia
William O. Weigle
Scripps Clinic and Research Foundation
La Jolla, California
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.
CONTEMPORARY TOPICS
IN IMMUNOBIOLOGY
6
VOLUME
Immunobiology of Oncogenic Viruses
EDITED BY
MICHAEL G. HANNA, JR.
Frederick Cancer Research Center
Frederick, Maryland
and
FRED RAPP
The Pennsylvania State University College of Medicine
Hershey, Pennsylvania
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Immunobiology of oncogenic viruses.
(Contemporary topics in immunobiology; v. 6)
Includes bibliographies and index.
1. Viral carcinogenesis. 2. Cancer-Immunological aspects. 3. Oncogenic viruses. I.
Hanna, Michael G., 1936· II. Rapp, Fred. III. Series. [DNLM: 1. Oncogenic
viruses-Immunology. WI C077 v. 6/QWI60.05 I33)
QR180.C632 vol. 6 [RC268.57) 574.2'9'08s 76·54885
ISBN 978· I ·4684·3053·0 ISBN 978· I ·4684·3051·6 (eBook) [616.9'94'0194)
DOl 10.1 007/978· I ·4684·3051·6
© 1977 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1977
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All righ ts 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
Contributors
Stuart A. Aaronson Laboratory of RNA Tumor Viruses, Viral Carcinogenesis Branch
National Cancer Institute
Bethesda, Maryland 20014
P. Bentvelzen Radiobiological Institute TNO
Rijswijk, The Netherlands
Maurice M. Black New York Medical College
Flower & Fifth A venue Hospitals
New York, New York 10029
Paul H. Black Infectious Disease Unit
Massachusetts General Hospital and Department of Medicine
Harvard Medical School
Boston, Massachusetts 02114
Dani P. Bolognesi Duke University Medical Center
Department of Surgery
Durham, North Carolina 27710
P. C. Creemers Radiobiological Institute TNO
Rijswijk, The Netherlands
Bert C. Del Villano Department of Immunopathology
Scripps Oinic and Research Foundation
La Jolla, California 92037
M. Essex Department of Microbiology
Harvard University School of Public Health
Boston, Massachusetts 02115
M. G. Hanna, Jr. Basic Research Program
NCI Frederick Cancer Research Center
Frederick, Maryland 21701
Martin S. Hirsch Infectious Disease Unit
Massachusetts General Hospital and Department of Medicine
Harvard Medical School
Boston, Massachusetts 02114
James N. Ihle Basic Research Program
NCI Frederick Cancer Research Center
Frederick, Maryland 21701
Stephen J. Kennel Department of Immunopathology
Scripps Oinic and Research Foundation
La Jolla, California 92037
v
vi Contributors
Richard A. Lerner Department of Immunopathology
Scripps Clinic and Research Foundation
La Jolla, California 92037
Paul H. Levine Laboratory of Viral Carcinogenesis
National Institutes of Health
National Cancer Institute
Bethesda, Maryland 20014
Max R. Proffitt Infectious Disease Unit
Massachusetts General Hospital and Department of Medicine
Harvard Medical School
Boston, Massachusetts 02114
Fred Rapp Department of Microbiology
and Specialized Cancer Research Center
The Milton S. Hershey Medical Center
The Pennsylvania State University
College of Medicine
Hershey, Pennsylvania 17033
Werner Schafer Max·Planck·Institut fur Virusforschung
Tuhingen, Germany
John R. Stephenson Laboratory of RNA Tumor Viruses, Viral Carcinogenesis Branch
National Cancer Institute
Bethesda, Maryland 20014
Satvir S. Tevethia Department of Pathology and Cancer Research Center
Tufts University School of Medicine
Boston, Massachusetts 02111
Preface
It has long been suspected, and recently confirmed, that there is an etiologic
relationship between several viruses and naturally occurring neoplasias. Virus
precursors in the form of nucleic acids or antigens have consistently been
associated with certain neoplasias. However, the role of these virus-specified
precursors in etiology remains obscure. Recent studies of virus-associated neo
plasias have led to advances in molecular techniques, which have yielded increas
ingly sensitive assays for detection of virus-specific nucleic acids, and which have
enabled the disruption of virus particles without concomitant loss in antigenicity
of the components. These procedures have, in turn, resulted in molecular probes
that allow more definitive evaluation of the host response to its virus and to the
tumor cell with which the virus or its precursors are associated. Evaluations of
the immune response and status of the host have provided important informa
tion about carcinogenesis and the tools for seroepidemiological studies of a
variety of cancers. These seroepidemiological studies have demonstrated that
several human cancers, e.g., Burkitt's lymphoma and nasopharyngeal carcinoma,
are probably virus-induced, and that antibodies that are diagnostic and prog
nostic for these diseases are detectable. The conclusion that feline leukemia is a
disease transmitted horizontally by a virus resulted primarily from immunologi
cal experiments. The important corollary to this conclusion is that the disease
can be prevented by removal of diseased animals from the population or by
antivirus vaccines; the latter approach has already been proven effective in
preventing the naturally occurring Marek's disease of chickens.
There is considerable evidence that the immune response plays a role in
neoplasia. Experimental studies indicate that, just as antigenic stimulation causes
activation of type C viruses, the graft-vs.-host reaction may result in a similar
phenomenon. Do such observations have a bearing on the increased incidence of
neoplastic disease in humans receiving organ transplants? It is tempting to
speculate that they do. Studies on natural immunity of lower animals to
oncornaviruses are providing data for similar studies in the human population.
The latter have been badly hindered by lack of appropriate reagents, but these
should soon be available.
vii
viii
The authors of chapters in this book have attempted to summarize the
status of research in the various areas of immunology concerned with virus-asso
ciated and virus-induced tumors. The results are often exciting and have led to a
far better understanding of the role of the immune response in governing the
onset and spread of virus-associated neoplasia. Extrapolation of the experimental
results to the human population will be intellectually and practically rewarding.
Interruption of the neoplastic process, at present, can only primarily be achieved
by combined modalities of treatment, including surgical and radiological proce
dures to reduce total tumor burden, and chemotherapy and immunotherapy to
eliminate residual tumor cells and to prevent their dissemination. It is hoped that
continued progress in the area of virus-associated neoplasias will result in
prevention, by direct vaccination or increase in immunologic capability, or
detection of cancer cells prior to development of a clinically detectable mass.
Frederick Cancer Research Center M. G. Hanna, Jr.
The Pennyslvania State University, Fred Rapp
College of Medicine
Contents
Chapter 1
Comparative Immunology of Carcinogenesis by DNA Viruses
Satvir S. Tevethia and Fred Rapp
I. Introduction .... 1
0 • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
II. Properties of Oncogenic DNA Viruses ........................ 2
III. Oncogenic Potential of DNA Viruses in Vivo ................... 3
A. Papovaviruses ........................................ 4
B. Adenoviruses ........................................ 7
C. Herpesviruses ........................................ 8
IV. Oncogenic Potential of Defective Genomes .................... 11
A. Oncogenicity of Defective Viruses Produced by Exogenous
Treatment .......................................... 11
B. Oncogenic Potential of Naturally Occurring Defective Genomes . 12
V. Neoplastic Transformation in Vitro by DNA Viruses ............. 14
A. Papovaviruses ........................................ 14
B. Adenoviruses ........................................ 17
C. Herpesviruses ........................................ 17
VI. Role of Virus Genome in Cell Transformation .................. 20
VII. Antigens Associated with DNA-Virus-Transformed Cells .......... 23
A. Intracellular Antigens .................................. 23
B. Antigens Associated with the Surface of DNA-Virus-Transformed
Cells ............................................... 28
VIII. Genetic Origin of DNA-Virus-Specified Antigens ................ 32
A. Origin of Intracellular Antigens .......................... 33
B. Origin of Cell-Surface Antigens .......................... 34
IX. Immune Response of the Host to DNA-Tumor-Virus-Induced
Antigens ............................................... 37
A. Papovaviruses (SV40 and Polyoma) ....................... 37
B. Other Papovaviruses and Adenoviruses ..........•.......... 42
C. Herpesviruses ........................................ 43
X. Role of DNA-Virus-Induced Antigens in Neoplasia .............. 46
ix
x Contents
XI. Conclusions ............................................ 49
XII. References ............................................. 50
Chapter 2
Immunity to Leukemia, Lymphoma, and Fibrosarcoma in Cats: A Case for
Immunosurveillance
M. Essex
I. Introduction ........................................... 71
II. Immunosurveillance Hypothesis ............................ 72
III. Feline Oncornaviruses .................................... 73
IV. Feline Oncornavirus-Associated Cell Membrane Antigen .......... 76
V. Laboratory-Induced and Naturally Occurring Tumors of Cats ...... 79
A. Horizontal Transmission ............................... 81
B. Immunosuppressive Potential of FeLV ., . . . . . . . . . . . . . . . . . .. 85
VI. Immune Response to Laboratory-Induced Tumors .............. 88
VII. Immune Response to Naturally Occurring Leukemia and Lymphoma 91
VIII. Summary and Conclusions ................................. 94
IX. References ............................................. 96
Chapter 3
Intracellular and Systemic Regulation of Biologically Distinguishable
Endogenous Type C RNA Viruses of Mouse Cells
Stuart A. Aaronson and John R. Stephenson
I. Introduction ........................................... 107
II. Evidence for Three Classes of Biologically Distinguishable
Endogenous Mouse Type C Viruses .......................... 108
III. Differential Activation of Endogenous Viruses ................. 111
IV. A Gene Affecting Expression of Class I Virus .................. 115
V. A Gene Influencing the Magnitude of Release of Class III
Endogenous Virus ....................................... 116
VI. Susceptibility to Exogenous Infection of Mouse Cells by Xenotropic
Virus ................................................. 117
VII. High-Titered Neutralizing Activity Directed Against Xenotropic
Virus in Normal Mouse Sera ............................... 120
VIII. Activation of Type C Viruses from Lymphoid Cells Following
Antigenic Stimulation .................................... 121
IX. Biological Functions of Endogenous Type C Viruses ............. 122
X. References ............................................. 123
