Table Of ContentThe
Togaviridae and
Flaviviridae
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
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 TOGAV IRIDAE AND FLA VIVIRIDAE
Edited by Sondra Schlesinger and Milton J. Schlesinger
The
Togaviridae and
Flaviviridae
Edited by
SONDRA SCHLESINGER
and
J.
MILTON SCHLESINGER
Washington University School of Medicine
St. Louis, Missouri
PLENUM PRESS • NEW YORK AND LONDON
library of Congress Catafoging in Publication Data
The Togaviridae and Flaviviridae.
(The Viruses)
Includes bibliographies and index.
1. Togaviruses. 2. Flaviviruses. I. Schlesinger. Sondra. II. Schlesinger. Milton]. III. Series.
QR415.5.T6 1986 616'.0194 86-4914
ISBN 978-1-4757-0787-8 ISBN 978-1-4757-0785-4 (eBook)
DOI 10.1007/978-1-4757-0785-4
© 1986 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1986
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
Contributors
Margo A. Brinton, The Wistar Institute of Anatomy and Biology, Phila
delphia, Pennsylvania 19104
Dennis T. Brown, Cell Research Institute and Department of Micro
biology, The University of Texas at Austin, Austin, Texas 78713
Lynn D. Condreay, Cell Research Institute and Department of Micro
biology, The University of Texas at Austin, Austin, Texas 78713
Diane E. Griffin, Departments of Medicine and Neurology, The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21205
Stephen C. Harrison, Department of Biochemistry and Molecular Biology,
Harvard University, Cambridge, Massachusetts 02138
Ari Helenius, Department of Cell Biology, Yale School of Medicine, New
Haven, Connecticut 06510
Margaret Kielian, Department of Cell Biology, Yale School of Medicine,
New Haven, Connecticut 06510
Thomas P. Monath, Division of Vector-Borne Viral Diseases, Center for
Infectious Diseases, Centers for Disease Control, Public Health Ser
vice, U.S. Department of Health and Human Services, Fort Collins,
Colorado 80522
James S. Porterfield, Sir William Dunn School of Pathology, University
of Oxford, Oxford OXI 3RE, England
Charles M. Rice, Division of Biology, California Institute of Technology,
Pasadena, California 91125
John T. Roehrig, Division of Vector-Borne Viral Diseases, Center for In
fectious Diseases, Centers for Disease Control, Public Health Ser
vice, U.S. Department of Health and Human Services, Fort Collins,
Colorado 80522
Milton J. Schlesinger, Department of Microbiology and Immunology,
Washington University School of Medicine, St. Louis, Missouri
63110
Sondra Schlesinger, Department of Microbiology and Immunology, Wash
ington University School of Medicine, St. Louis, Missouri 63110
v
vi CONTRIBUTORS
Ellen G. Strauss,.Division of Biology, California Institute of Technology,
Pasadena, California 91125
James H. Strauss, Division of Biology, California Institute of Technology,
Pasadena, California 91125
Barbara G. Weiss, Department of Microbiology and Immunology, Wash
ington University School of Medicine, St. Louis, Missouri 63110
Preface
The publication of this volume of The Viruses entitled The Togaviridae
and Flaviviridae comes at an appropriate time. The structure and rep
lication strategies of these viruses are now known to be sufficiently di
verse to warrant the removal of flaviviruses from the Togaviridae family
and establish them as an independent family. Flaviviridae have a special
place in the history of virology. The prototype virus-yellow fever virus
was the first virus to be identified as the cause of a human disease. Some
of the history of this discovery is described in Chapter 1 of this volume;
in Chapter 10 the complete sequence of the RNA genome of the virus is
presented. This sequence not only defines the primary structure of the
viral proteins, it also clarifies the mechanism of translation of the fla
vivirus genome. Knowledge of the sequence of the structural proteins of
these viruses represents an important step in the potential goal of using
purified flavivirus glycoproteins as vaccines. Many of the chapters in this
volume focus on the structure and replication of the Togaviridae. These
viruses have provided valuable models for studies in cell biology, partic
ularly with regard to the cotranslational and posttranslational steps re
quired for the synthesis and localization of membrane glycoproteins. Fur
thermore, Togaviridae have been pivotal in our growing understanding
of how enveloped viruses enter and exit from cells.
The broad outlines of the structure and gene expression of Togavir
idae and Flaviviridae are known, but important questions remain. We
have relatively little information about the replication of their genomes.
Togaviridae synthesize four non structural proteins. What are their func
tions? How is the synthesis of the subgenomic 26S RNA regulated? Major
gaps also exist in our understanding of the interactions between these
viruses and their hosts. In both families, virulent and avirulent strains
of the same virus exist. What actually determines virulence? Is it the
ability of a virus to infect a sensitive target cell or are other factors in
volved? Defective interfering particles can be important in maintaining
persistent infections in cultured cells. Do they playa role in modulating
an infection in an organism? Genetic traits of the host can be a major
vii
viii PREFACE
factor in the outcome of an infection as evidenced by the ability of a
single gene to control the sensitivity or resistance of mice to flaviviruses.
What is this gene product and how does it exert its effect? We have com
piled this volume as a compendium of what is known about these viruses,
but we hope it also serves as an impetus to investigate the unsolved
problems.
Sondra Schlesinger
Milton J. Schlesinger
St. Louis, Missouri
Contents
Chapter 1
Comparative and Historical Aspects of the Togaviridae
and Flaviviridae
Tames S. Porterfield
I. Introduction ..................................... 1
II. Yellow Fever .................................... 2
A. Early History ................................. 2
B. Carlos J. Finlay and the Walter Reed Commission. . . . . 2
C. Yellow Fever Commissions of the Rockefeller
FoundatioQ. ................................... 3
D. Asibi Virus and the 17D Yellow Fever Vaccine ....... 3
III. Early Studies on Viral Encephalitides . . . . . . . . . . . . . . . . . . 5
IV. Arthropod-Borne Viruses ........................... 5
A. Antigenic Relationships among Arboviruses ......... 6
B. Serological Groups A and B ...................... 7
V. Viral Classification and Nomenclature ................ 8
VI. Arbovirus Study Group: Togaviruses and Togaviridae ..... 9
VII. Non-Arthropod-Borne Togaviruses ................... 11
VIII. Contribution of the World Health Organization ......... 14
IX. Contribution of the American Committee on Arthropod-
Borne Viruses .................................... 14
X. Impact of Molecular Biology on Viral Classification ...... 15
XI. Flaviviridae as a Separate Family ..................... 15
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Chapter 2
Alphavirus Structure
Stephen C. Harrison
I. Introduction ..................................... 21
II. General Properties ................................ 21
ix
x CONTENTS
A. Radial Organization ............................ 22
B. Glycoprotein Shell ............................. 23
C. Lipid Bilayer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
D. Core (Nucleocapsid) ............................ 29
E. Hexagonal Glycoprotein Arrays .................... 30
III. Virion Assembly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Chapter 3
Structure and Replication of the Alphavirus Genome
Ellen G. Strauss and Tames H. Strauss
I. Introduction ..................................... 35
II. Structure of the Alphavirus Genome .................. 36
A. Physical Structure ............................. 36
B. Genome Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
III. Nonstructural Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
A. Translation and Processing . . . . . . . . . . . . . . . . . . . . . . . 43
B. Opal Codon .................................. 44
C. Functions of Nonstructural Proteins ............... 46
IV. Structural Proteins ................................ 47
A. Translation and Processing . . . . . . . . . . . . . . . . . . . . . . . 47
B. Functions of Structural Proteins . . . . . . . . . . . . . . . . . . . 49
C. Mapping of Temperature-Sensitive Mutants. . . . . . . . . . 51
V. Replication and Transcription of Viral RNA ............ 52
A. In Vivo Studies of RNA Replication ............... 52
B. In Vitro Studies of RNA Replication . . . . . . . . . . . . . . . 54
C. Genetic Studies of Replicase Functions ............. 57
D. Host-Cell Proteins as Components of the
Viral Replicase ................................ 59
E. Conserved Sequences in Alphavirus RNAs . . . . . . . . . . . 59
F. Cyclization of Alphavirus RNAs .................. 65
G. Alphavirus Defective Interfering RNAs ............. 67
VI. Evolution of the Alphavirus Genome . . . . . . . . . . . . . . . . . . 69
A. Evolution within the Genus Alphavirus . . . . . . . . . . . . . 69
B. Codon Usage in Alphaviruses . . . . . . . . . . . . . . . . . . . . . 73
C. Evolution within the Family Togaviridae . . . . . . . . . . . . 75
D. Relationship of Alphaviruses to Other RNA Viruses ... 76
VII. Concluding Remarks .............................. 81
References .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
