15
The Papovaviridae Volume 2 TIlE PAPILLOMA VIRUSES

TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

  • Upload
    others

  • View
    1

  • Download
    0

Embed Size (px)

Citation preview

Page 1: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

The Papovaviridae Volume 2 TIlE PAPILLOMA VIRUSES

Page 2: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

THE VIRUSES

Series Editors HEINZ FRAENKEL-CONRAT, University of California

Berkeley, California

ROBERT R. WAGNER, University of Virginia School of Medicine

Charlottesville, Virginia

THE VIRUSES: Catalogue, Characterization, and Classification Heinz Fraenkel-Conrat

THE ADENOVIRUSES Edited by Harold S. Ginsberg

THE HERPESVIRUSES Volumes 1-3 • Edited by Bernard Roizman Volume 4 • Edited by Bernard Roizman and Carlos Lopez

THEPAPOVAVIRIDAE Volume 1 • Edited by Norman P. Salzman Volume 2 • Edited by Norman P. Salzman and Peter M. Howley

THE PARVOVIRUSES Edited by Kenneth I. Berns

THE PLANT VIRUSES Volume 1 • Edited by R. I. B. Francki Volume 2. Edited by M. H. V. Van Regenmortel and Heinz Fraenkel-Conrat

THE REOVIRIDAE Edited by Wolfgang K. Joklik

THE RHABDOVIRUSES Edited by Robert R. Wagner

THE TOGA VIRIDAE AND FLAVIVIRIDAE Edited by Sondra Schlesinger and Milton J. Schlesinger

THE VIROIDS Edited by T. o. Diener

Page 3: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

The Papovaviridae Volume 2 THE PAPILLOMAVIRUSES

Edited by

NORMAN P. SALZMAN and

PETER M. HOWLEY National Institutes of Health Bethesda, Maryland

PLENUM PRESS • NEW YORK AND LONDON

Page 4: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

Library of Congress Cataloging in Publication Data

(Revised for volume 2)

The papovaviridae.

(The Viruses) Volume 2 edited by Norman P. Salzman and Peter M. Howley. Includes bibliographies and index. Contents: v. 1. The polyomaviruses- The papillomaviruses. 1. Papovaviruses-Collected works. I. Salzman, Norman P. II. Howley, Peter M.

III. Series: The Viruses. [DNLM: 1. Papovaviridae. QW 165.5.P2 P218j QR406.P36 1986 576'.6484 86-15160 ISBN 978-1-4757-0586-7 ISBN 978-1-4757-0584-3 (eBook) DOI 10.1007/978-1-4757-0584-3

© 1987 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1987

A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013

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

Page 5: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

Contributors

Eberhard Amtmann, Institute for Virus Research, German Cancer Re­search Center, 6900 Heidelberg, Federal Republic of Germany

Harri Ahola, Department of Medical Genetics, University of Uppsala, Biomedical Center, S-751 23 Uppsala, Sweden

Carl C. Baker, Laboratory of Tumor Virus Biology, National Cancer In­stitute, Bethesda, Maryland 20892

Daniel DiMaio, Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510

Peter M. Howley, Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892

Robert F. LaPorta, Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York, Stony Brook, New York 11794

Jorge Moreno-Lopez, Department of Veterinary Microbiology (Virology), Swedish University of Agricultural Sciences, Biomedical Center, S-751 23 Uppsala, Sweden

Carl Olson, Department of Veterinary Science, University of Wisconsin, Madison, Wisconsin 53706

Gerard Orth, Unite des Papillomavirus, Unite INSERM 190, Institut Pas­teur, 75724 Paris Cedex IS, France

Ulf Pettersson, Department of Medical Genetics, University of Uppsala, Biomedical Center, S-751 23 Uppsala, Sweden

Herbert Pfister, Institut fiir Klinische Virologie, Universitiit Erlangen­Niirnberg, 0-8520 Erlangen, Federal Republic of Germany

Richard Schlegel, Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892

Achim Schneider, Sektion fiir Gyniikologische Zytologie und Histologie, Universitiits-Frauenklinik, 7900 Ulm, Federal Republic of Germany

Bettie M. Steinberg, Department of Otolaryngology, Long Island Jewish Medical Center, New Hyde Park, New York 11042

v

Page 6: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

vi CONTRIBUTORS

Arne Stenlund, Department of Medical Genetics, University of Uppsala, Biomedical Center, S-751 23 Uppsala, Sweden; Present address: De­partment of Molecular Biology, University of California, Berkeley, California 94720

Lorne B. Taichman, Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York, Stony Brook, New York 11794

Klaus Wayss, Institute for Pathology, German Cancer Research Center, 6900 Heidelberg, Federal Republic of Germany

Felix o. Wettstein, Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90024

Harald zur Hausen, Deutsches Krebsforschungszentrum, 6900 Heidel­berg, Federal Republic of Germany

Page 7: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

Preface

In recent years there has been an explosion in research on the papillo­maviruses. The viral nature of human warts was first suggested 80 years ago by Ciuffo, who demonstrated transmission using cell-free filtrates. Shope described the first papillomavirus over 50 years ago as the etiologic agent in infectious papillomatosis in rabbits. Subsequent studies by Rous established that benign rabbit papillomas induced by this virus could progress to carcinomas when treated with specific nonviral cofactors. Despite these rich beginnings, the papillomavirus field lay virtually dor­mant until the late 1970s because no one was able to propagate these viruses in culture successfully. In the late 1970s the molecular cloning of the papillomavirus genomes permitted investigators to partially cir­cumvent this obstacle to their progress. The cloning of the viral genomes permitted the standardization of viral reagents and provided sufficient material to begin a systematic evaluation of the biology of this group of viruses.

This volume contains a series of chapters designed to provide a his­torical perspective on this field and to review the current state of research involving the papillomaviruses. Chapters 1 and 2 serve as introductory chapters, providing a general description and overview of the papillo­maviruses and a historical perspective. Chapters 3-5 cover the molecular biology and cell biology of the papillomaviruses, focusing on transcrip­tion, gene expression in epithelial cells, and viral transformation. The rabbit and the Mastomys natalensis provide animal models for studying carcinogenic progression and are covered in Chapters 6 and 7. In humans, HPVs have been associated with cutaneous carcinomas in patients with epidermodysplasia verruciformis and with anogenital carcinomas; these topics are reviewed in Chapters 8 and 9. Laryngeal papillomas are asso­ciated with the same HPV types seen in the genital tract and are also capable of malignant progression, as discussed in Chapter 10. The viral DNA of the bovine papillomavirus type 1 has been developed into a

vii

Page 8: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

viii PREFACE

mammalian cell cloning vector based on its ability to remain as a stable plasmid in transformed cells, and its use as a cloning vector is reviewed in Chapter 11. Finally, an appendix is included presenting an analysis of sequences of the viral genomes available at the time this book was com­pleted.

Norman P. Salzman Peter M. Howley

Page 9: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

Contents

Chapter 1

Papillomaviruses: General Description, Taxonomy, and Classification

Herbert Pfister

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 II. Properties of the Virions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

A. Particle Structure and Protein Composition ............ 2 B. Nucleic Acid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

III. Biological Properties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 A. Characteristics of the Benign Tumors . . . . . . . . . . . . . . . . . . 5 B. Immune Response of the Host. . . . . . . . . . . . . . . . . . . . . . . . . 9 C. Malignant Conversion-General Aspects . . . . . . . . . . . . . . . 10

IV. Classification and Nomenclature. . . . . . . . . . . . . . . . . . . . . . . . . . 13 V. Description of Virus Types. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

A. Human Papillomaviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 B. Bovine Papillomaviruses ..... . . . . . . . . . . . . . . . . . . . . . . . . . 22 C. Other Papillomaviruses from Animals ................. 25

VI. Evolutionary Aspects. . . . . . . . . . . . .. . . . . . . .. . . . . . . . ... . . . . . 27 A. Papillomaviruses and Miopapovaviruses . . . . . . . . . . . . . . . . 27 B. Evolution of Papillomaviruses . . . . . . . . . . . . . . . . . . . . . . . . . 27 C. Papillomaviruses from Epidermodysplasia Verruciformis 28 D. Reservoir of Papillomaviruses ......................... 29

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

ix

Page 10: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

x CONTENTS

Chapter 2

Animal Papillomas: Historical Perspectives

Carl Olson

I. Canine Oral Papillomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 II. Shope Rabbit Papilloma .................................. 42

III. Equine Papillomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 IV. Bovine Papillomatosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 V. Papillomatosis in Sheep .................................. 58

VI. Oral Papillomatosis of Rabbits ............................ 58 VII. Deer Fibromatosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

VIII. European Elk Papillomaviruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 IX. Viral Papillomatosis in Other Animals. . . . . . . . . . . . . . . . . . . . . 60

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

Chapter 3

Organization and Expression of Papillomavirus Genomes

Ull Pettersson, Harri Ahola, Arne Stenlund, and Jorge Moreno-Lopez

I. Introduction............................................. 67 II. General Properties of Papillomavirus Genomes . . . . . . . . . . . . . 68

III. The Genome of BPV-l ........... '" .... . .. . ..... . .. . . ... . 71 A. Organization of the E (Transforming)-Region ........... 71 B. Organization of the L-Region . . . . . . . . . . . . . . . . . . . . . . . . . . 72 C. The Noncoding Region ............................... 72 D. Transcriptional Signals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 E. The Origin of DNA Replication ....................... 74

IV. Comparative Anatomy of Papillomavirus Genomes ......... 75 A. Features of the HPV-la Genome.... ... . .... . ... . .... .. 75 B. Features of the HPV-6b Genome.... .... .... . .... ...... 77 C. Features of the CRPV Genome ........................ 79 D. Features of Other Papillomavirus Genomes.... ..... .... 81

V. Predicted Functions of Papillomavirus Proteins. . . . . . . . . . . . . 82 VI. Transcriptional Organization of Papillomavirus Genomes . . . 84

A. RNAs Expressed in Rodent Cells Transformed by BPV-l 85 B. mRNAs Transcribed in Virus-Producing BPV-I-Induced

Fibropapillomas ...................................... 93 C. The Transcription Map of the BPV -1 Genome Is

Incomplete. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 D. Transcriptional Organization of the CRPV Genome. . ... 97

Page 11: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

CONTENTS xi

E. Common Features between BPV-1 and CRPV Transcription ........................................ 100

F. Transcriptional Organization of Human Papillomavirus Genomes ............................................ 102

VII. Conclusions............................................. 102 References .................................................. " 103

Chapter 4

The Expression of Papillomaviruses in Epithelial Cells

Lorne B. Taichman and Robert F. LaPorta

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109 II. Epithelium and Keratinization ............................ 110

III. Behavioral Classification of PVs . . . . . . . . . . . . . . . . . . . . . . . . . .. 116 IV. Histological Characteristics of PV-Induced Lesions ......... 117 V. Transformation.......................................... 121

VI. Vegetative Viral Growth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 123 VII. Cytopathic Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 127

VIII. Expression of PV in Cultured Keratinocytes . . . . . . . . . . . . . . .. 128 IX. Expression of PV in Malignant Cells. . . . . . . . . . . . . . . . . . . . . .. 131 X. Conclusions ............................................. 133

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 134

Chapter 5

Papilloma virus Transformation

Peter M. Howley and Richard Schlegel

I. Introduction............................................. 141 II. Transformation Biology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 143

III. Transcription............................................ 147 IV. Transforming Functions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 150

A. Genetics............................................. 150 B. E6 Gene .......................... ,. . .. . . . . . . .... . . .. 153 C. E5 Gene.. . . . . . . . . . .. . . . . .. . .... . . . . .. . .. . . . . . . . ... .. 154 D. E2 Gene. . . . . . . . . . . .. . . . ... . . ... . . . . .. . ... . . . . . . . .. .. 156

V. Plasmid Maintenance Functions. . . . . . . . . . . . . . . . . . . . . . . . . .. 158 A. Cis Elements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 159 B. Trans Functions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 160

VI. Summary and Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 160 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 163

Page 12: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

xii CONTENTS

Chapter 6

Papillomaviruses and Carcinogenic Progression I: Cottontail Rabbit (Shope) Papillomavirus

Felix O. Wettstein

I. Introduction............................................. 167 II. Biological Properties of the System. . . . . . . . . . . . . . . . . . . . . . .. 168

A. Virus Multiplication and Tumor Induction . . . . . . . . . . . .. 168 B. Tumor Progression ................................... 170 C. Interaction with Chemical Carcinogens . . . . . . . . . . . . . . .. 171 D. Regression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 172

III. Molecular Aspects of the System. . . . . . . . . . . . . . . . . . . . . . . . .. 173 A. The Virus and Viral Genome . . . . . . . . . . . . . . . . . . . . . . . . .. 173 B. State of the Viral DNA ............................... 176 C. Viral Transcripts ..................................... 179 D. Conclusion .......................................... 180

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 183

Chapter 7

Papillomaviruses and Carcinogenic Progression II: The Mastomys natalensis Papillomavirus

Eberhard Amtmann and Klaus Wayss

I. The Animal System...... ...... ......... ..... ..... ..... .. 187 II. Epithelial Skin Tumors in Mastomys .............. '" . .... 188

III. Identification of MnPV as the Causative Agent of Skin Tumors ................................................. 189

IV. Characterization of the Virus ............................. 190 V. Persistence of MnPV Genomes in Normal Tissu~s... ....... 191

VI. Accumulation of Viral DNA in Normal Skin during Aging.. 192 VII. MnPV Genome Expression in Tumors.. ... .. ... ..... . ..... 194

VIII. Induction of MnPV by Tumor Promoters ................. " 195 IX. Induction of Antibodies against MnPV in Mastomys ........ 197

References .................................................... 198

Chapter 8

Epidermodysplasia Verruciformis

Gerard Orth

I. Introduction............................................. 199 II. Clinical Aspects of EV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 201

Page 13: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

CONTENTS xiii

A. Clinical Course of the Disease. . . . . . . . . . . . . . . . . . . . . . . .. 201 B. Morphology of EV Lesions ............................ 202

III. Histology and Ultrastructure of EV Lesions ................ 204 A. Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204 B. Malignant Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 206

IV. Genetic Factors in EV ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 207 V. Immunological Factors in EV ............................. 209

A. Humoral Immunity ................................... 210 B. Cell-Mediated Immunity. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 211 C. Regression of EV ..................................... 212

VI. HPV Types Associated with EV ........................... 212 A. Multiplicity and Specificity. . . . . . . . . . . . . . . . . . . . . . . . . .. 212 B. Biochemical Properties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 214 C. HPV Infection in EV Patients. . . . . . . . . . . . . . . . . . . . . . . . .. 223

VII. Role of HPVs in EV Carcinomas. . . . . . . . . . . . . . . . . . . . . . . . . .. 224 A. HPV Types Found in EV Cancers . . . . . . . . . . . . . . . . . . . . .. 224 B. Physical State of HPV Genomes . . . . . . . . . . . . . . . . . . . . . .. 225 C. Expression of HPV Genomes ..... . . . . . . . . . . . . . . . . . . . .. 227

VIII. HPVs and Skin Neoplasia in Non-EV Patients. . . . . . . . . . . . .. 227 A. Immunodepression or Immunosuppression . . . . . . . . . . . .. 227 B. General Population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 229

IX. In Vitro Studies on EV HPVs . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231 X. Questions Raised by EV .................................. 231

A. Plurality of HPVs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231 B. Control of HPV Infection ............................. 232 C. Cofactors in HPV Oncogenesis ........................ 233 D. Mechanisms of Tumor Progression .................... 234

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 235

Chapter 9

The Role of Papillomaviruses in Human Anogenital Cancer

Harald zur Hausen and Achim Schneider

I. Introduction and Historical Aspects ....................... 245 II. Isolation of Genital Papillomaviruses and Their

Characterization ......................................... 248 III. Biology of Genital Papillomavirus Infections ............... 250 IV. HPV DNA Sequences in Cell Lines ........................ 255 V. State of Viral DNA in Benign and Malignant Lesions ....... 256

VI. Interaction of Papillomavirus Infections with Initiators in Malignant Conversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 257

VII. Association of Malignant Tumors with Genital Papillomavirus Infections at Extragenital Sites ............. 258

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 259

Page 14: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

xiv CONTENTS

Chapter 10

Laryngeal Papillomas: Clinical Aspects and in Vitro Studies

Bettie M. Steinberg

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 265 II. Clinical Description. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 266

III. Treatment ............................................... 269 A. Physical Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 270 B. Surgical Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 270 C. Medical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 270 D. Immunotherapy ...................................... 271

IV. Pathology................................................ 272 V. Molecular and Cellular Biology. . . . . . . . . . . . . . . . . . . . . . . . . . .. 275

A. Etiology ............................................. 275 B. Tissue Culture Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 283

VI. Laryngeal Papillomas and Laryngeal Cancer . . . . . . . . . . . . . . .. 286 VII. Major Unanswered Questions. " ........... , .............. 287 References .................................................... 289

Chapter 11

Papillomavirus Cloning Vectors

Daniel DiMaio

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 293 II. Transformation by Bovine Papillomavirus . . . . . . . . . . . . . . . . .. 294

III. Development of BPV-1 Vectors ............................ 297 IV. Expression of Genes Cloned on BPV-1 ..................... 301

A. Human I3-Globin Gene .............................. " 302 B. Metallothioneins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 303 C. Hepatitis B Surface Antigen . . . . . . . . . . . . . . . . . . . . . . . . . .. 304 D. Human I3-Interferon Gene ........................... " 305 E. Mouse Mammary Tumor Virus. . . . . . . . . . . . . . . . . . . . . . .. 308 F. Polypeptide Hormones ................................ 309

G. Other Genes ......................................... 309 V. Stability of BPV-1 Recombinants ........................ " 310

VI. FutureDirections ........................................ 312 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 315

Appendix

Sequence Analysis of Papillomavirus Genomes

Carl C. Baker

I. Papillomavirus Sequences. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321 II. Restriction Site Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 352

Page 15: TIlE PAPILLOMA VIRUSES3A978-1-4757... · 2017. 8. 28. · TIlE PAPILLOMA VIRUSES . THE VIRUSES Series Editors HEINZ FRAENKEL-CONRAT, University of California Berkeley, California

CONTENTS xv

III. Genome Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 366 IV. Protein Comparisons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 367

A. E1 ORF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 371 B. E20RF .............................................. 371 C. E40RF .............................................. 372 D. ES ORF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 377 E. E60RF .............................................. 377 F. E70RF.............................................. 377

G. Ll ORF .............................................. 379 H. L20RF .............................................. 379

References .................................................... 384

Index ......................................................... 387