EPSTEIN-BARR VIRUS AND ASSOCIATED DISEASES

DEVELOPMENTS IN MEDICAL VIROLOGY

Yechiel Becker, Series Editor Julia Hadar, Managing Editor

Levine, et al (eds.), Epstein-Barr Virus and Associated Diseases (1985)

EPSTEIN-BARR VIRUS AND ASSOCIATED DISEASES

Proceedings of the First International Symposium on Epstein-Barr Virus-Associated Malignant Diseases (Loutraki, Greece-September 24-28, 1984)

edited by

P.H. Levine D. V. Ablashi G.R. Pearson S.D. Kottaridis

~ ., Martinus Nijhoff Publishing a member of the Kluwer Academic Publishers Group Boston/Dordrecht/Lancaster

Distributors for North America: Kluwer Academic Publishers 190 Old Derby Street Hingham, MA 02043, USA

Distributors for the UK and Ireland: KIuwer Academic Publishers MTP Press Limited Falcon House, Queen Square Lancaster LAI IRN, UK

Distributors for all other countries: KIuwer Academic Publishers Group Distribution Centre P.O. Box 322 3300 AH Dordrecht, THE NETHERLANDS

The figure on the cover is from Proc Natl Acad Sci USA, 81:4652, 1984, and is used with permission. It also appears on page 447 of this book.

Library of Congress Cataloging in Publication Data International Symposium on Epstein-Barr Virus­

Associated Malignant Diseases (1 st : 1984 : Loutraki, Greece)

Epstein-Barr virus and associated diseases.

(Developments in medical virology) Includes bibliographies. I. Epstein-Barr virus-Congresses. 2. Nasopharynx­

Cancer-Congresses. 3. Oncologic viruses-Congresses. 4. Virus diseases-Congresses. I. Levine, P.H. (Paul H.) II. Title. III. Series. [DNLM: 1. Epstein­Barr Virus-immunology-congresses. 2. Epstein-Barr Virus-pathogenicity-congresses. 3. Immunologic Deficiency Syndromes-congresses. 4. Medical Oncology­congresses. 5. Nasopharyngeal Neoplasms-congresses. 6. Tumor Virus Infections-congresses. QW 165.5.H3 1616 1984e] QR400.2.E68157 1984 576' .6484 85-15484

ISBN-13 :978-1-4612-9641-6 DOl: I 0.1 007/978-1-4613-2625-0

e-ISBN-13 :978-1-4613-2625-0

Copyright © 1985 by Martinus Nijhoff Publishing, Boston Softcover reprint of the hardcover I st edition 1985

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without written permission of the publisher, Martinus Nijhoff Publishing, 190 Old Derby Street, Hingham, Massachusetts 02043.

SERIES PREFACE PREFACE ACKNOWLEDGMENTS

CONTENTS

IMMUNODEFICIENCY DISEASES

1. Association of Epstein-Barr Virus and Lymphoproliferative Diseases in Immune Deficient Persons D. T. PurtUo

2. Relapsing, Recurrent and Chronic Infectious Mononucleosis in the Normal Host S.E. Straus

3. Immune Assessment of Patients with Chronic Active EBV Infection (CAEBV) J.F. Jones, S.B. Straus, G. Tosato, R.A. Kibler, M. Hicks, D. Lucas, 0. Preble, T. Lawley, G. Armstrong, G. Pearson and R.M. Blaese

4. Reversal of Common Variable Hypogammaglobulinemia­Associated Suppressor Cell Activity by Specific Carbohydrates G. Tosato, S.B. Pike and R.M. Blaese

5. Unusual Primary Tumors of Brain and Lungs Associated with Epstein-Barr Virus (EBV) J. Joncas, F. Ghibu, N. Lapointe, L. Begin, J. Michaud, P. Simard, P. Benoit, G. Rivard, J. Demers and R. Raymond

6. Lytic, Non-Transforming Epstein-Barr Virus (EBV) from Two Patients with Chronic Active EBV Infection C. Alfieri, F. Ghibu and J. Joncas

7. Brief Communication: The Significance of Antibodies Against the Epstein-Barr Virus-Specific Membrane Antigen gp250 in Acute and Latent EBV Infections W. JUg and H. Wolfe

EBV-ASSOCIATED MALIGNANCIES

8. The Epidemiology of Epstein-Barr Virus-Associated Malignancies P.H. Levine

9. Genetic Aspects of EBV-Associated Malignancies M. Simons 10. Pathology of Epstein-Barr Virus (EBV)-Associated Disease

(the Lymphatic System) G.R.F. Krueger 11. The "Family Study" Approach to Investigating the Role of

Genetic Factors in Nasopharyngeal Carcinoma S.J. Bale, A.B. Bale and P.H. Levine

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12. An EBV-Associated Salivary Gland Cancer A.P. Lanier, S. Krishnamurthy, S.E. Clift, K. T. Kline, G. W. Bornkamm, W. Henle, A. Gown and D. Thorning

13. Nasopharyngeal Carcinoma: Early Detection and IgA­Related pre-NPC Condition. Achievements and Prospectives Y. Zeng and G. de The

14. Evaluation of Epstein-Barr Virus Serologic Analysis in North American Patients with Nasopharyngeal Carcinoma and in Comparison Groups H.B. Neel, III, G.R. Pearson and W.F. Taylor

15. Use of Epstein-Barr Virus Serology in the Diagnosis of Nasopharyngeal Carcinoma in Malaysia M. Yadav, N. Malliha, A. W. Norhanom and U. Prasad

16. An Analysis of the Relationship Between Clinical Pathology and Serological Level of EB Virus VCA-IgA Antibody in Nasopharyngeal Carcinoma P.S. Huang, Y.D. Chen and Y. Y. Shen

17. Brief Communication: Fossa of Rosenmuller: The Site for Initial Development of Carcinoma of the Nasopharynx U. Prasad, J. Singh and R. Patmanathan

18. Brief Communication: Carcino-Embryonic Antigen (CEA) in Nasopharyngeal Carcinoma and Chronic Nasopharyngitis Y. Y. Shen and P. S. Huang

19. Brief Communication: HLA-Antigens in NPC Patients from a Low-Risk Area (Cologne, FRG) G. Bertram, J. Kruger and K. Sesterhenn

MOLECULAR BIOLOGY OF EBV

20. Persistence and Expression of the Epstein-Barr Virus Genome in Latent Infection and Growth Transformation of Lymphocytes E. KiefJ, K. Hennessy, T. Dambaugh, T. Matsuo, S. Fennewald, M. Heller, L. Petti and M. Hummel

21. An Epstein-Barr Virus-Determined Nuclear Antigen Encoded by a Region within the EcoRI A Fragment of the Viral Genome L. Rymo and G. Klein

22. An EBV RNA with a Repetitive Spliced Structure M. Bodescot, B. Chambraud and M. Perricaudet

23. Characterization of an EBV-Associated Protein Kinase E. Fowler

24. Characterization of the Genes within the BamHI Fragment of Epstein-Barr Virus DNA that may Determine the Fate of Viral Infection J. Sample, A. Tanaka, G. Lancz and M. Nonoyama

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25. Effects of Tunicamycin on Binding of Epstein-Barr Virus N. Ba/achandran and L.M. Hutt-Fletcher

26. Brief Communication: Structure and Expression of the Epstein-Barr Virus Genome P.J. Farrell, J. Dyson, P. Tuffnell, M. Biggin, T. Gibson, A. Bankier, G. Hudson, G. Hatfull, S. Satchwell and B. Barrell

27. Brief Communication: Antibody Response to Epstein-Barr Virus-Specific DNase in Thirteen Patients with Naso­pharyngeal Carcinoma J. Y. Chen, R.P. Beas/ey, C.S. Chien and C. S. Yang

28. Brief Communication: Recent Developments in Nucleic Acid Hybridization H. Wolf, S. Gu, M. Haus and U. Leser

MECHANISMS OF EBV TRANSFORMATION

29. The Host-Cell Range of the Epstein-Barr Virus R. G/aser 30. Epstein-Barr Virus (EBV) Growth Transformation is

Associated with an Alteration in C-MYC Chromatin Structure W.H. Schubach, B.H. Steiner and M. Birkenbach

31. Study of Nucleosomal Organization of Chromatin in EBV Producer and Non-Producer Cells V. Zongza and S.D. Kottaridis

32. Novel Biological Functions Associated with Epstein-Barr Virus DNA B.E. Griffin, D. King and L. Karran

33. EBV DNA Content and Expression in Nasopharyngeal Carcinoma N. Raab-Traub, D. Huang, C. S. Yang and G. Pearson

34. Transformation of Human Lymphocytes by Coinfection with EBV DNA and Transformation-Defective Virions D.J. Vo/sky, B. Vo/sky, M. Hedeskog, F. Sinangil and T.G. Gross

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35. Epstein-Barr Virus-Activating Substance(s) from Soil Y. Ito, 383 H. Tokuda, H. Ohigashi, K. Koshimizu and Y. Zeng

36. Hydrocortisone Enhancement of both EBV Replication and 392 Transformation of Human Cord Lymphocytes D. V. Ab/ashi, J. Whitman, J. Dah/berg, G. Armstrong and J. Rhim

37. Brief Communication: Detection of EBNA and Rescue of 402 Transforming EBV in Megakaryocyte Cells Established in Culture D. Morgan and D. V. Ab/ashi

EBV PROTEINS

38. Advances in the Identification of EBV-Specific Proteins: 411 An Overview G.R. Pearson

39. Bacterially Synthesized EBNA as a Reagent for Enzyme 426

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Linked Immunosorbent Assays G. Milman, D.K. Ades, M-S Cho, S.c. Hartman, G.S. Hayward, A.L. Scott and S.D. Hayward

40. Epstein-Barr Virus Nuclear Antigen (EBNA): Antigenicity of 436 the Molecule Encoded by the Bam HI K Fragment of the EBV Genome M.J. Allday and A.J. MacGillivray

41. The Use of Antibodies Against Synthetic Peptides for 446 Studying the EBV Nuclear Antigen J. Dillner, L. Eliasson, L. Stern as, B. Kallin, G. Klein and R.A. Lerner

42. Characterization of Two Forms of the 72,000 MW EBNA and 456 a Cross-Reacting Cellular Protein J. Luka, T. Kreojsky, T. C. Spelsberg, G.R. Pearson, K. Hennessey and E. Kiejj

43. Identification of EBV-Specific Antigens Following Micro- 466 injection of Sub genomic DNA Fragments A. Boyd, J. Stoerker, J. Holliday and R. Glaser

44. Localization of Epstein-Barr Virus Early Antigen (EA) by 477 Electron Microscopy M. Kishishita, Y. Ito, J. Luka and G.R. Pearson

45. Selection and Production by Genetechnological Methods of 485 Medically Relevant EBV-related Antigens H. Wolf, M. Motz, R. Kuhbeck, R. Seibl, G.J. Bayliss, S. Modrow and J. Fan

46. Identification of Multiple Epstein-Barr Virus Nuclear 495 Antigens T.B. Sculley, P.J. Walker, D.J. Moss and J.H. Pope

47. Brief Communication: Production of Human Monoclonal 504 Antibodies by EBV Immortalization J. Paire and C. Desgranges

IMMUNOLOGY

48. Cellular Immunity in EBV Infections J.H. Pope 49. T Cell Responses to Epstein-Barr Virus Infection

A.B. Rickinson 50. Epstein-Barr Virus and Immunosuppression J. Menezes and

S.K. Sundar 51. In Vitro Immunogenicity of Human Lymphoid Tumour Cell

Lines D.J. Moss, J.A. Staples, S.R. Burrows, J. Ryan and T.B. Sculley

52. Monocyte Contrasuppression of EBV-Immune Regulatory T Cells G. Tosato, S.E. Pike and R.M. Blaese

53. Analysis of Intratumoral Lymphocyte Subsets in Patients with Undifferentiated Nasopharyngeal Carcinoma T. Tursz, P. Herait, M. Lipinski, G. Ganem, M. C. Dokhelar, C. Carlu, C. Micheau and G. de The

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54. Potential Usefulness of Isoprinosine as an Immunostimulating 580 Agent in EBV-Associated Disorders: In Vitro Studies S.K. Sundar, G. Barile and J. Menezes

55. Mechanisms of Expression of a Burkitt Lymphoma-Associated 588 Antigen (Globotriaosylceramide) in Burkitt Lymphoma and Lymphoblastoid Cell Lines J. Wiels, E.H. Holmes, N. Cochran, S.l. Hakomori and T. Tursz

CONTROL OF EBV-ASSOCIATED MALIGNANT DISEASE

56. Prevention of EB Virus-Associated Malignant Diseases 603 M.A. Epstein

57. A Perspective on Treatment of EBV Infection States 619 J.S. Pagano

58. Clinical and Pathobiological Features of Burkitt's 631 Lymphoma and their Relevance to Treatment I. Magrath

59. Management of Nasopharyngeal Carcinoma A. T. Huang, 644 I.R. Crocker, S.R. Fisher and M.J. Wallman

60. Treatment of Nasopharyngeal Carcinoma with the Antiviral 660 Drug 9-[(2-Hydroxyethoxymethyl)] Guanine: A Case Report J. W. Sixbey, E. Thompson and E. C. Douglass

61. EBV-specific Transfer Factor in the Treatment of African 666 Burkitt's Lymphoma: A Pilot Study F.K. Nkrumah, G. Pizza, D. Viza, J. Neequaye, C. DeVinci and P.H. Levine

62. Brief Communication: The Teatment of Nasopharyngeal 673 Carcinoma (NPC) J.H. Ho

SPECIAL LECTURE

63. Epstein-Barr Virus: Past, Present and Future G. Henle and W. Henle

LIST OF PARTICIPANTS

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PREFACE TO THE SERIES, DEVELOPMENTS IN MEDICAL VIROLOGY

It is my pleasure to introduce the first volume in our new series, Developments in Medical Virology. This series is planned to add another dimension to our understanding of the processes involving viruses as pathogens of cells and organisms. Our series Developments in Molecular Virology is devoted to the basic molecular aspects of virus replication, while Developments in Veterinary Virology deals with viral disease processes in domestic animals.

It is hoped that Developments in Medical Virology will provide advanced information on the understanding of virus diseases of man. The current volume deals in depth with various aspects of Epstein-Barr virus. Forth­coming volumes will be devoted to viruses affecting various organs and will also focus on different illnesses caused by a specific family of viruses.

Certain volumes in the current series are intended to complement their counterparts in Developments in Molecular Virology, so as to update our knowledge of human virus diseases and the practices used in their control.

I would like to express my appreciation to the editors of this book and to all those already engaged in the preparation of volumes to appear in the future.

Yechiel Becker Series Editor

PREFACE

It has been slightly more than two decades since the Epstein-Barr virus (EBV) was discovered by Prof. M.A. Epstein and his colleagues at the University of Bristol in their search for the causative agent of Burkitt's lymphoma. For several years EBV was a "virus in search of a disease." The first documentation that EBV was pathogenic for humans was in 1969 when Drs. Gertrude and Werner Henle identified it as the causative agent for infectious mononucleosis. Seroepidemiologic and biochemical studies subsequently linked EBV to Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), and more recently to the X-linked lymphoproliferative syndrome. With its widespread pattern of infection and a predilection for producing clinical signs and symptoms in only certain individuals, EBV has provided a model for many other candidate oncogenic viruses, including papilloma viruses, herpes simplex, and HTLV/LAV.

In 1975, an international workshop was sponsored by the National Cancer Institute to address the problem of EBV production, thus facilitating basic research on the virus. This proved to be the last international meeting on EBV for almost a decade. In the past, progress in both clinical and basic research on EBV has been presented in two types of international meetings, the international herpesvirus workshops devoted primarily to basic research on both human and animal herpesviruses, and the international symposia on NPC, in which EBV-related studies were interspersed with clinical, epidemiologic and other etiologic aspects of this important human neoplasm. Because of the rapid advances in both basic and applied research on this widely investigated virus, scientists in several countries initiated a meeting in September 1985 to review the current status of the field and to propose new areas of research. Attracting clinicians, epidemiologists, immuno-virologists, geneticists and workers in other areas of carcinogenesis, the meeting proved to be a stimulating forum for fruitful discussion.

The continual progress in understanding the biochemistry as well as the biology of EBV is apparent from the manuscripts presented at this symposium and appearing in this book. EBV, a ubiquitous virus which may cause many illnesses still unidentified, has long merited the attention and concentrated discussion permitted by

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this First International Symposium. It is our hope that the documentation of the recent progress in studies of this virus and the observation of areas still needing concentrated attention (such as the laboratory investigation of nasopharyngeal carcinoma, which has still resisted attempts to grow the undifferentiated tumor cells in tissue culture), will provide a guideline as well as a status report to new investigators interested in pursuing the enigma of why a ubiquitous virus can produce so many different clinical outcomes. It is apparent from the diverse problems being studied and the many unanswered questions still being raised that there are still many opportunities for clinicians and basic scientists to find new leads regarding the pathogenesis and control of this important human virus.

ACKNOWLEDGMENTS

The Editors wish to thank the following for their support and cooperation which helped immeasurably in making this symposium a success.

ABBOT LABORATORIES U.S.A. ADVANCED BIOTECHNOLOGY U.S.A. ADAMS-CHILCOTT S.A. AGMARTIN S.A. AMERICAN KIDNEY FUND U.S.A. BACAKOS S.A. BANTIN AND KINGMAN LTD. BEHRINGWERKE A G B.I.B.E. ANAPLIOTIS S.A. BAYER RESEARCH LABORATORIES W. GERMANY BIOTECH RESEARCH LABORATORIES, INC. U.S.A. BRISTOL HELLAS BURROUGHS WELCOME CO. U.S.A. ELI-LILLY HELLAS ESSEX HELLAS GREEK ANTICANCER INSTITUTE GREEK ANTICANCER SOCIETY HARTELLAS S.A. JANSSEN PHARMACEUTICA A.E.B.E. KALIFRONAS S.A. KYRIAKIDIS S.A. LITTON BIONETICS INC. MERCK, SHARPE AND DOHME RESEARCH LABORATORIES U.S.A. MINISTRY OF CULTURE AND SCIENCES (GREtCE) MINISTRY OF HEALTH (GREECE) N.D. VARELAS S.A. NATIONAL CANCER INSTITUTE (USA) NATIONAL TOURIST ORGANIZATION OF GREECE PRINIOTAKIS S.A. SHOWA UNIVERSITY RESEARCH INSTITUTE FOR

BIOMEDICINE IN FLORIDA SMITH, KLINE AND FRENCH U.S.A. SQUIBB S.A. VIANEX S.A.

Credits

We also thank Ms. Adriana Cabrales, Ms. Stephanie Coleman, Mrs. Kristine L. Ablashi and Mrs. Harriet Huebner, for their assistance in preparing manuscripts for publication.

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