BASIC VIROLOGY In Memoriam Edward K. Wagner (May 4, 1940 to January 21, 2006) It was one of those telephone calls that you do not want to receive. Each of us, that weekend in late January, heard of the untimely passing of our colleague, co-author, collaborator, mentor, and friend, Ed Wagner. Ed will be remembered for his many contributions to the teaching of virology and for his research contributing to our understanding of the intricacies of the herpesviruses. From his graduate work at MIT, through his postdoctoral research at the University of Chicago, and on to his professorship at the University of California, Irvine, Ed was a passionate champion for the most rigorous and critical thinking and the most dedicated teaching, setting a standard for the discipline of virology. Beyond the laboratory and the classroom, Ed loved life to the fullest, with his family and friends. The last time we were together as a writing team, in the fall of 2005, we all remember an intense day of work in a conference room at UCI, followed by an evening of touring some of Ed’s favorite haunts in the Southern California coastal towns he called home. It is with those thoughts etched into our memories that we dedicate this edition of Basic Virology to Edward K. Wagner. Basic Virology Third Edition Edward K. Wagner Department of Molecular Biology and Biochemistry University of California, Irvine Martinez J. Hewlett Department of Molecular and Cellular Biology University of Arizona David C. Bloom Department of Molecular Genetics and Microbiology University of Florida David Camerini Department of Molecular Biology and Biochemistry University of California, Irvine © 1999, 2004, 2008 by Blackwell Publishing BLACKWELL PUBLISHING 350 Main Street, Malden, MA 02148-5020, USA 9600 Garsington Road, Oxford OX4 2DQ, UK 550 Swanston Street, Carlton, Victoria 3053, Australia The right of Edward K. Wagner, Martinez J. Hewlett, David C. Bloom, and David Camerini to be identifi ed as the Authors of this Work has been asserted in accordance with the UK Copyright, Designs, and Patents Act 1988. 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, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs, and Patents Act 1988, without the prior permission of the publisher. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks, or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. First edition published 1999 Second edition published 2004 Third edition published 2008 by Blackwell Publishing Ltd 1 2008 Library of Congress Cataloging-in-Publication Data Basic virology / Edward K. Wagner . . . [et al.]. – 3rd ed. p. ; cm. Rev. ed. of: Basic virology / Edward K. Wagner, Martinez J. Hewlett. 2nd ed. 2004. Includes bibliographical references and index. ISBN-13: 978-1-4051-4715-6 (pbk. : alk. paper) ISBN-10: 1-4051-4715-6 (pbk. : alk. paper) 1. Viruses. 2. Virus diseases. 3. Virology. 4. Medical virology. I. Wagner, Edward K. II. Wagner, Edward K. Basic virology. [DNLM: 1. Virus Diseases–virology. 2. Genome, Viral. 3. Virus Replication. 4. Viruses–pathogenicity. WC 500 B311 2008] QR360.W26 2008 579.2–dc22 2007019839 A catalogue record for this title is available from the British Library. Set in 10.5 on 12.5 pt Adobe Garamond by SNP Best-set Typesetter Ltd., Hong Kong Printed and bound in Singapore by Markono Print Media Pte Ltd The publisher’s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp processed using acid-free and elementary chlorine-free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. For further information on Blackwell Publishing, visit our website: www.blackwellpublishing.com Brief Contents Preface xxi Acknowledgments xxix PART I VIROLOGY AND VIRAL DISEASE 1 Chapter 1 Introduction – The Impact of Viruses on Our View of Life 3 Chapter 2 An Outline of Virus Replication and Viral Pathogenesis 15 Chapter 3 Virus Disease in Populations and Individual Animals 27 Chapter 4 Patterns of Some Viral Diseases of Humans 41 PART II BASIC PROPERTIES OF VIRUSES AND VIRUS– CELL INTERACTION 63 Chapter 5 Virus Structure and Classifi cation 65 Chapter 6 The Beginning and End of the Virus Replication Cycle 79 Chapter 7 H ost Immune Response to Viral Infection – The Nature of the Vertebrate Immune Response 97 Chapter 8 Strategies to Protect Against and Combat Viral Infection 119 PART III WORKING WITH VIRUS 145 Chapter 9 Visualization and Enumeration of Virus Particles 147 Chapter 10 Replicating and Measuring Biological Activity of Viruses 155 Chapter 11 Physical and Chemical Manipulation of the Structural Components of Viruses 173 Chapter 12 Characterization of Viral Products Expressed in the Infected Cell 193 Chapter 13 Viruses Use Cellular Processes to Express their Genetic Information 213 PART IV REPLICATION PATTERNS OF SPECIFIC VIRUSES 243 Chapter 14 Replication of Positive-sense RNA Viruses 245 Chapter 15 Replication Strategies of RNA Viruses Requiring RNA-directed mRNA Transcription as the First Step in Viral Gene Expression 273 Chapter 16 Replication Strategies of Small and Medium-sized DNA Viruses 303 vi BRIEF CONTENTS Chapter 17 Replication of Some Nuclear-replicating Eukaryotic DNA Viruses with Large Genomes 331 Chapter 18 Replication of Cytoplasmic DNA Viruses and “Large” Bacteriophages 359 Chapter 19 Retroviruses: Converting RNA to DNA 381 Chapter 20 Human Immunodefi ciency Virus Type 1 (HIV-1) and Related Lentiviruses 399 Chapter 21 Hepadnaviruses: Variations on the Retrovirus Theme 413 PART V VIRUSES: NEW APPROACHES AND NEW PROBLEMS 433 Chapter 22 The Molecular Genetics of Viruses 435 Chapter 23 Molecular Pathogenesis 463 Chapter 24 Viral Bioinformatics and Beyond 473 Chapter 25 Viruses and the Future – Problems and Promises 485 Appendix Resource Center 501 Technical Glossary 507 Index 533 Contents Preface xxi Preface to the second edition xxii Preface to the third edition xxii Text organization xxiii Specifi c features of this text designed to aid instructors and students in pursuing topics in greater depth xxvi Depth of coverage xxvi Sources for further study xxvi The Internet xxvii Chapter outlines xxvii Case studies xxvii Review material xxvii Glossary xxvii Acknowledgments xxix PART I VIROLOGY AND VIRAL DISEASE 1 CHAPTER 1 Introduction – The Impact of Viruses on Our View of Life 3 The science of virology 3 The effect of virus infections on the host organism and populations – viral pathogenesis, virulence, and epidemiology 4 The interaction between viruses and their hosts 6 The history of virology 7 Examples of the impact of viral disease on human history 8 Examples of the evolutionary impact of the virus–host interaction 9 The origin of viruses 9 Viruses have a constructive as well as destructive impact on society 12 Viruses are not the smallest self-replicating pathogens 13 Questions for Chapter 1 14 CHAPTER 2 An Outline of Virus Replication and Viral Pathogenesis 15 Virus replication 15 Stages of virus replication in the cell 17 Pathogenesis of viral infection 19 Stages of virus-induced pathology 19 viii CONTENTS Initial stages of infection – entry of the virus into the host 20 The incubation period and spread of virus through the host 21 Multiplication of virus to high levels – occurrence of disease symptoms 23 The later stages of infection – the immune response 24 The later stages of infection – virus spread to the next individual 24 The later stages of infection – fate of the host 24 Questions for Chapter 2 25 CHAPTER 3 Virus Disease in Populations and Individual Animals 27 The nature of virus reservoirs 27 Some viruses with human reservoirs 28 Some viruses with vertebrate reservoirs 30 Viruses in populations 30 Viral epidemiology in small and large populations 30 Factors affecting the control of viral disease in populations 33 Animal models to study viral pathogenesis 34 A mouse model for studying poxvirus infection and spread 35 Rabies: where is the virus during its long incubation period? 37 Herpes simplex virus latency 37 Murine models 39 Rabbit models 40 Guinea pig models 40 Questions for Chapter 3 40 CHAPTER 4 Patterns of Some Viral Diseases of Humans 41 The dynamics of human–virus interactions 42 The stable association of viruses with their natural host places specifi c constraints on the nature of viral disease and mode of persistence 42 Classifi cation of human disease-causing viruses according to virus–host dynamics 44 Viral diseases leading to persistence of the virus in the host are generally associated with viruses having long associations with human populations 44 Viral diseases associated with acute, severe infection are suggestive of zoonoses 48 Patterns of specifi c viral diseases of humans 49 Acute infections followed by virus clearing 49 Colds and respiratory infections 49 Infl uenza 49 Variola 49 Infection of an “accidental” target tissue leading to permanent damage despite effi cient clearing 50 Persistent viral infections 50 Papilloma and polyomavirus infections 50 Herpesvirus infections and latency 52 Other complications arising from persistent infections 52 Viral and subviral diseases with long incubation periods 53 Rabies 53 CONTENTS ix HIV–AIDS 53 Prion diseases 54 Some viral infections targeting specifi c organ systems 54 Viral infections of nerve tissue 54 Examples of viral encephalitis with grave prognosis 55 Rabies 55 Herpes encephalitis 55 Viral encephalitis with favorable prognosis for recovery 56 Viral infections of the liver (viral hepatitis) 56 Hepatitis A 57 Hepatitis B 57 Hepatitis C 57 Hepatitis D 57 Hepatitis E 58 Questions for Chapter 4 58 Problems for Part I 59 Additional Reading for Part I 61 PART II BASIC PROPERTIES OF VIRUSES AND VIRUS–CELL INTERACTION 63 CHAPTER 5 Virus Structure and Classifi cation 65 The features of a virus 65 Viral genomes 69 Viral capsids 69 Viral envelopes 72 Classifi cation schemes 72 The Baltimore scheme of virus classifi cation 75 Disease-based classifi cation schemes for viruses 75 The virosphere 77 Questions for Chapter 5 78 CHAPTER 6 The Beginning and End of the Virus Replication Cycle 79 Outline of the virus replication cycle 79 Viral entry 80 Animal virus entry into cells – the role of the cellular receptor 80 Mechanisms of entry of nonenveloped viruses 83 Entry of enveloped viruses 84 Entry of virus into plant cells 85 Injection of bacteriophage DNA into Escherichia coli 87 Nonspecifi c methods of introducing viral genomes into cells 89 Late events in viral infection: capsid assembly and virion release 89 Assembly of helical capsids 89 Assembly of icosahedral capsids 92 Generation of the virion envelope and egress of the enveloped virion 93 Questions for Chapter 6 96 CHAPTER 7 Host Immune Response to Viral Infection – The Nature of the Vertebrate Immune Response 97 The innate immune response – early defense against pathogens 98 Toll-like receptors 99