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The Epstein-Barr Virus PDF

466 Pages·1979·13.6 MB·English
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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. This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use, a fee is payable to the publisher, the amount of the fee to be determined by agreement with the publisher. © by Springer-Verlag Berlin Heidelberg 1979 Softcover reprint of the hardcover 1s t edition 1979 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, than such names are exempt from the relevant protective laws and regulations and therefore free for general use. 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

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