The Epstein-Barr Virus

466 Pages·1979·13.6 MB·English

by  Ph.D., M.D., D.Sc., F.R.S., B. G. Achong (auth.), F.R.C. Path., B. G. Achong M.B., B.Ch., B.A.O., M.D. (eds.)

The Epstein-Barr Virus
Edited by M. A. Epstein and B. G. Achong
With 72 Figures and 29 Tables
Springer-Verlag
Berlin Heidelberg New York 1979
M.A. Epstein, M.A., M.D., Ph.D., D.Sc., F.R.C. Path., F.R.S.
B.G. Achong, M.B., B.eh., B.A.O., M.D.
Department of Pathology, The Medical School, University of
Bristol, University Walk, Bristol BS8 1T D (England)
ISBN-13: 978-3-642-67238-5 e-ISBN-13: 978-3-642-67236-1
DOl: 10.1007/978-3-642-67236-1
Library of Congress Cataloging in Publication Data. Main entry under title: The
Epstein-Barr virus. Bibliography: p. Includes index. 1. Epstein-Barr virus. 2.
Lymphocyte transformation. 3. Viral genetics. 4. Viral carcinogenesis. 1. Epstein,
Michael Anthony. II. Achong, B.G., 1928-. QR400.2.E68E65 616.01'9479-4370.
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© by Springer-Verlag Berlin Heidelberg 1979
Softcover reprint of the hardcover 1s t edition 1979
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Wiesbaden. 2123/3140-543210
Preface
The Epstein-Barr virus was discovered 15 years ago. Since
that time an immense body of information has been accumu-
lated on this agent which has come to assume great signifi-
cance in many different fields of biological science. Thus, the
virus has very special relevance in human medicine and
oncology, in tumor virology, in immunology, and in mole-
cular virology, since it is the cause of infectious mononu-
cleosis and also the first human cancer virus, etiologically
related to endemic Burkitt's lymphoma and probably to
nasopharyngeal carcinoma. In addition, continuous human
lymphoid cell lines initiated and maintained by the transform-
ing function of the virus genome provide a laboratory tool
with wide and ever-growing applications.
Innumerable papers on the Epstein-Barr virus have ap-
peared over recent years and reports of work with this agent
now constitute a veritable flood. The present book provides
the first and only comprehensive, authoritative over-view of
all aspects of the virus by authors who have been the original
and major contributors in their particular disciplines.
A complete and up-to-date survey of this unique and
important agent is thus provided which should be of great
interest to experts, teachers, and students engaged in cancer
research, virology, immunology, molecular biology, epide-
miology, and cell culture. Where topics have been dealt with
from more than one of these viewpoints, some inevitable
overlap and duplication has resulted; although this has been
kept to a minimum, it has been retained in some places
because of positive usefulness.
M. A. Epstein
B. G. Achong
List of Contents
M. A. Epstein and B. G. Achong
1 Introduction: Discovery and General Biology of the Virus 1
A. Introduction . . . 2
B. Discovery of EBV . 3
C. General Biology . 4
M. A. Epstein and B. G. Achong
2 Morphology of the Virus and of Virus-Induced
Cytopathologic Changes 23
A. Introduction . . . . . . . . . . . . 24
B. Virus Morphology . . . . . . . . . 24
C. Virus-Induced Cytopathologic Changes 29
D.Comment ............ . 33
1. Ernberg and G. Klein
3 EB Virus-Induced Antigens 39
A. Introduction . . . . . 40
B. Antigen Detection Methods 41
C. Membrane Antigen . . . . 43
D. The Early Antigen Complex 45
E. The Viral Capsid Antigen . 47
F. The EBV Nuclear Antigen. 48
G. Lymphocyte-Detected Membrane Antigen 51
H. Antigen Expression in EBV-Carrying Cell Lines 51
1. Expression of EBV Antigens During the Viral Cycle 52
w. Henle and G. Henle
4 Seroepidemiology of the Virus 61
A. Identification of EBV as a New Human Herpes Group
Virus . . . . . . . . . . . . . . . . . 62
B. Serologic Association of EBV with Burkitt's
Lymphoma and Other Diseases. . . . . . 63
C. The Seroepidemiology of Burkitt's Lymphoma 66
D. The Seroepidemiology of Nasopharyngeal Carcinoma 69
E. The Seroepidemiology of Infectious Mononucleosis. 71
F. Seroepidemiologic Observations in Other Diseases 72
G. Concluding Remarks . . . . . . . . . . . . .. 73
VIII LIST OF CONTENTS
Y. Becker
5 Biochemistry of the Virus and Its Effects on the Metabolism
of Infected Cells. . . . . . . . . . . . . . . . .. 79
A. Introduction: B Lymphocytes, the Natural Host of
EBV. . . . . . . . . . . . . . . . . . . . .. 82
B. Molecular Composition of EB Virions. . . . . .. 83
C. Biochemical Consideration of the Resident EBV DNA
in Lymphoblastoid Cells. . . . . . . . . . . .. 88
D. Biochemical Events Leading to the Release of EBV
DNA from Control of Host-Cell Mechanisms . .. 90
E. Biochemical Aspects of EBV DNA Replication and
Transcription. . . . . . . . . . .- . . . . . 96
F. Biochemical Properties of EBV Nuclear Antigen
(EBNA) . . . . . . . . . . . . . . . . . . 99
G. Biochemical Aspects of Infection of Lymphoblastoid
Cells and Leukocytes with EBV. . 100
H. Transformation of Cells with DNA . 102
1. Discussion. . . . . . . . . . . . 102
J. S. Pagano and J. E. Shaw
6 Molecular Probes and Genome Homology. 109
A. General Introduction . . 110
B. Technology . . . . . . 111
C. What We Have Learned. 132
D. Prospects ... . 138
E. Unifying Concept ... . 141
H. zur Hausen
7 Biochemical Detection of the Virus Genome 147
A. Adams
8 The State of the Virus Genome in Transformed Cells and Its
Relationship to Host Cell DNA . . . 155
A. Introduction . . . . . . . . . . . . . . . . .. 156
B. Types of EBV-Transformed Cells. . . . . . . .. 156
C. Models for the Maintenance of Latent EBV Genomes
in Transformed Cells . . . . . . . . . . . . .. 157
D. First Experimental Evidence for Free, Nonintegrated
EBV Genomes in Raji Cells . . . . . . . . . .. 160
E. Possible Forms of Free, Nonintegrated EBV Genomes 161
F. Detailed Analysis of the Free, Nonintegrated EBV
Genomes in Raji Cells. . . . . . . . . . . . .. 163
LIST OF CONTENTS IX
G. Detection of EBV DNA Covalently Bound to Host
DNA in Raji Cells . . . . . . . . . . . . . .. 166
H. State of the EBV Genomes in Other Cells . . . .. 169
I. Replication of the Latent EBV DNA in Transformed
Cells . . . . . . . . . . . . . . . . . . . .. 174
J. Association of EBV DNA with Chromosomes . .. 177
K. The EBV Genome and the Evolution of Burkitt's
Lymphoma. . . . . . . . . . . . . . . . . .. 178
J. 1. Strominger and D. Thorley-Lawson
9 Early Events in Transformation of Human Lymphocytes
by the Virus. . . . . . . . . 185
A. Recognition and Adsorption. . 186
B. Penetration of Virus. . . . . . 188
C. Expression of Viral Information 190
D. Integration of EBV Genomes. . 197
E. Expression of Information from Integrated Genomes 200
J. H. Pope
10 Transformation by the Virus In Vitro. 205
A. Introduction . . . . . . . . . . 206
B. General Description of Transformation 206
C. Viral Characteristics. . . . . . . 208
D. Target Cells and Their Properties. 209
E. Infectivity Assays. . . . 211
F. Virus-Cell Relationships. . . 212
G. Cellular Interactions. . . . . 215
H. Inhibition of Transformation. 215
I. Role of In Vitro Transformation by EBV in the
Establishment of Lymphoblastoid Cell Lines in
Primary Culture of Human Tissues . . . . . 217
J. Effects of EBV Transformation on Karyotype 218
K. Conclusion. . . . . . . . . . . . . . . . 218
K. Nilsson
11 The Nature of Lymphoid Cell Lines and Their Relationship
to the Virus. . . . . . . . . . . . . . . . . . .. 225
A. Introduction . . . . . . . . . . . . . . . . . . 227
B. Provisional Classifications of Hematopoietic Cell Lines 229
C. "Spontaneous" Establishment of Permanent
EBV-Carrying Lymphoid Cell Lines. . . . . . . . 233
x LIST OF CONTENTS
D. Markers for Clonality. . . . . . . 236
E. Phenotypic Characteristics of EBV-Carrying
Lymphoid Cell Lines ....... 238
F. Chromosome Studies on EBV-Carrying Lymphoid
Cell Lines . . . . . . . . . . . . . . . . . .. 259
G. Phenotypic Stability During Long-Term Cultivation. 262
H. EBV Genome-Negative Hematopoietic Cell Lines. 263
1. Concluding Remarks . . . . . . . . . . . . .. 266
B. Hampar
12 Activation of the Viral Genome In Vitro. 283
A. Introduction . . . . . . . . . . . 284
B. Properties of Human Lymphoblastoid Cell Lines 284
C. State of the Virus Genome in Lymphoblastoid Cells. 285
D. Spontaneous Activation . . . . 286
E. Activation Induced by Chemicals 287
F. Virus Expression in Hybrid Cells 290
G. Concluding Remarks . . . . . 292
G. Henle and W. Henle
13 The Virus as the Etiologic Agent of Infectious M ononucleo-
sis. . . . . . . . . . . . . . . . . . . . . . . . 297
A. Evidence for the Etiologic Role of EBV in Infectious
Mononucleosis . . . . . . . . . . . . . 298
B. Implications of the Serologic and Virologic
Observations in Infectious Mononucleosis . 303
C. Facts and Speculations Regarding Pathogenesis. 307
M. A. Epstein and B. G. Achong
14 The Relationship of the Virus to Burkitt's Lymphoma. 321
A. Introduction . . . . . . . . . . . . . . 322
B. Burkitt's Lymphoma . . . . . . . . . . 322
C. The Virus and African Burkitt's Lymphoma 324
D. Sporadic Burkitt's Lymphoma . . . . . 328
E. Oncornaviruses and Burkitt's Lymphoma 329
F. Discussion . . . . . . . . . . . . . . 329
LIST OF CONTENTS XI
G. Klein
15 The Relationship of the Virus to Nasopharyngeal
Carcinoma . . . . 339
A. Introduction . . . . . . . . . . . . . . . 340
B. Histopathology. . . . . . . . . . . . . . 340
C. EBV-Related Serology in Nasopharyngeal Carcinoma 341
D. EBV Genomes in Nasopharyngeal Carcinoma .. 342
E. Biologic Activity of Nasopharyngeal Carcinoma -
Associated EBV . . . . . . . . 344
F. Disease-Related Serologic Studies. 345
G. Concluding Remarks . . . . . . 346
G. Miller
16 Experimental Carcinogenicity by the T6irus in Vivo 351
A. Introduction . . . . . . . . . . . . . . . 352
B. Virus Factors in Tumorigenesis. . . . . . . 353
C. Host Factors in Experimental Carcinogenicity 355
D. Pathology of the Experimental Disease . . . 357
E. EBV Genome in the Experimental Tumors. . 361
F. EBV-Specific and Heterophil Antibody Responses of
Experimentally Infected Animals . . . . . . . .. 364
G. Special Features of Transformed Marmoset Cells. . 365
H. Significance of Experimental Carcinogenicity by EBV 368
I. Future Work with EBV in Primates. . . . . . .. 369
F. Deinhardt and J. Deinhardt
17 Comparative Aspects: Oncogenic Animal Herpesviruses 373
A. Introduction . . . . . . . . . . . . . 374
B. Herpesviruses of Cold-Blooded Animals. 377
C. Herpesviruses of Warm-Blooded Animals 379
D. Conclusions . . . . . . . . . . . . . 400
G. de-The
18 Demographic Studies Implicating the Virus in the Causation
of Burkitt's Lymphoma; Prospects for Nasopharyngeal
Carcinoma . . . . . . . . . . . . . . . . . . .. 417
A. Introduction . . . . . . . . . . . . . . . . . . 418
B. Epidemiologic Characteristics of EBV Infection and of
the Associated Tumors . . . . . . . . . . . . . 418
XII LIST OF CONTENTS
C. The IARC Prospective Study of Burkitt's Lymphoma
in Uganda and the Causative Role of the Virus. 423
D. Prospects for the Epidemiologic Approach in
Nasopharyngeal Carcinoma . . . . . . . . . 431
E. Intervention as the Final Step in Proving Causality 433
F. Conclusions . . . . . . . . . . . . . . . " 435
M. A. Epstein
19 Vaccine Control of EE Virus-Associated Tumors 439
A. Introduction . . . . . . . . . . . . 440
B. EBV as the Cause of a Human Cancer . . 440
C. A Vaccine to Prevent EBV Infection . . . 441
D. The Vaccine Prevention of EBV-Re1ated Tumors 444
E. Discussion . . . . . . . . . . . . . . . . . 445
Subject Index . . . . . . . . . . . . . . . . . . . . 449