P R I NC I P L E S O F FOURTH EDITION ALANJ CANN
CONTENTS Preface to the fourth edition Preface to the third edition Preface to the second edition xii Preface to the first edition Chapter 1 Introduction Viruses are Distinct from Living Organisms The History of Virology Living Host Systems Cell Culture Methods Serological/Immunological Methods 9 Ultrastructural Studies 12 'Molecular Biology 18 Further Reading 24 Chapter 2 Particles 3 The Function and Formation of Virus Particles 2 Capsid Symmetry and Virus Architecture 28 Enveloped Viruses Complex Virus Structures Protein-Nucleic Acid Interactions and Genome Packaging 2 Virus Receptors:Recognition and Binding 分 Other Interactions of the Virus Capsid with the Host Cell Summary Further Reading 父
CONTENTS Preface to the fourth edition x Preface to the third edition xi Preface to the second edition xii Preface to the first edition xiii Chapter 1 Introduction 1 Viruses are Distinct from Living Organisms 2 The History of Virology 3 Living Host Systems 5 Cell Culture Methods 7 Serological/Immunological Methods 9 Ultrastructural Studies 12 ‘Molecular Biology’ 18 Further Reading 24 Chapter 2 Particles 25 The Function and Formation of Virus Particles 25 Capsid Symmetry and Virus Architecture 28 Enveloped Viruses 39 Complex Virus Structures 42 Protein–Nucleic Acid Interactions and Genome Packaging 49 Virus Receptors: Recognition and Binding 53 Other Interactions of the Virus Capsid with the Host Cell 53 Summary 54 Further Reading 54
vContents Chapter 3 Genomes 56 The Structure and Complexity of Virus Genomes Molecular Genetics 59 Virus Genetics Virus Mutants Suppression Genetic Interactions between Viruses Nongenetic Interactions between Viruses 87 Large'DNA Genomes 73 Small'DNA Genomes Positive-Strand rna viruses Negative-Strand RNA Viruses Segmented and Multipartite Virus Genomes Reverse Transcription and Transposition Evolution and Epidemiology 呢0 Further Reading Chapter 4 Replication 1 Overview of Virus Replication Investigation of Virus Replication 184 The Replication Cycle 10 Further Reading Chapter 5 Expression Expression of Genetic Information 81 Control of Prokaryote Gene Expression Control of Expression in Bacteriophage A Control of Eukaryote Gene Expression 138 Transcriptional Co ntrol of Expression Posttranscriptional Control of Expression Further Reading 164 Chapter 6 Infection Virus Infections of Plants 18 Immune Responses to Virus Infections in Animals Viruses and Apoptosis Interferons Evasion of Immune Responses by Viruses 181 Virus-Host Interactions 183
Chapter 3 Genomes 56 The Structure and Complexity of Virus Genomes 56 Molecular Genetics 59 Virus Genetics 62 Virus Mutants 64 Suppression 67 Genetic Interactions between Viruses 68 Nongenetic Interactions between Viruses 71 ‘Large’ DNA Genomes 73 ‘Small’ DNA Genomes 75 Positive-Strand RNA Viruses 78 Negative-Strand RNA Viruses 82 Segmented and Multipartite Virus Genomes 84 Reverse Transcription and Transposition 87 Evolution and Epidemiology 98 Summary 101 Further Reading 101 Chapter 4 Replication 102 Overview of Virus Replication 102 Investigation of Virus Replication 104 The Replication Cycle 108 Summary 129 Further Reading 129 Chapter 5 Expression 131 Expression of Genetic Information 131 Control of Prokaryote Gene Expression 132 Control of Expression in Bacteriophage l 133 Control of Eukaryote Gene Expression 138 Transcriptional Control of Expression 150 Posttranscriptional Control of Expression 155 Summary 163 Further Reading 164 Chapter 6 Infection 165 Virus Infections of Plants 166 Immune Responses to Virus Infections in Animals 169 Viruses and Apoptosis 174 Interferons 177 Evasion of Immune Responses by Viruses 181 Virus–Host Interactions 183 viii Contents
Contents ix The Course of Virus Infections 192 Virus Vectors and Gene Therapy 199 Chemotherapy of Virus Infections Summary 20% Further Reading 20 Chapter 7 Pathogenesis 208 Mechanisms of Cellular Injury 2 Viruses and Immunodeficiency 212 Virus-Related Diseases 22 Bacteriophages and Human Disease Cell Transformation by Viruses Viruses and Cancer New and Emergent Viruses 6 Zoonoses 2 Bioterrorism Summary Further Reading 248 Chapter 8 Subviral Agents:Genomes without Viruses, Viruses without Genomes 249 Satellites and Viroids 249 Prions 2 Summary Further Reading 287 Appendix 1 Glossary and Abbreviations 269 Appendix 2 Classification of Subcellular Infectious Agents 281 Appendix 3 The History of Virology Index 300
The Course of Virus Infections 192 Virus Vectors and Gene Therapy 199 Chemotherapy of Virus Infections 200 Summary 206 Further Reading 206 Chapter 7 Pathogenesis 208 Mechanisms of Cellular Injury 210 Viruses and Immunodeficiency 212 Virus-Related Diseases 221 Bacteriophages and Human Disease 224 Cell Transformation by Viruses 225 Viruses and Cancer 236 New and Emergent Viruses 240 Zoonoses 246 Bioterrorism 247 Summary 248 Further Reading 248 Chapter 8 Subviral Agents: Genomes without Viruses, Viruses without Genomes 249 Satellites and Viroids 249 Prions 253 Summary 267 Further Reading 267 Appendix 1 Glossary and Abbreviations 269 Appendix 2 Classification of Subcellular Infectious Agents 281 Appendix 3 The History of Virology 294 Index 300 Contents ix
PREFACE TO THE FOURTH EDITION In addition to complete updating,this edition of Principles of Moleclar Virology con tains a number of additions to the text and illustrations;for example,new infor- mation on topics such as SARS and bioterrorism.However,most changes have been made to the enclosed CD.In addition to complete reformatting.the content has been completely revised and we have been able to include for the first time a series of animations covering important topics such as capsid symmetry,virus repli- cation and immune recognition and killing of virus-infected cells.There is also a new interactive self-assessment quiz for each chapter so you can judge for yourself your knowledge of virology. I would like to extend my thanks to the staff of Elsevier for their assistance during the preparation of the book.I am confident that readers will find this edition as useful as the previous ones. Alan I.Cann University of Leicester,UK alan.cam @leicester.ac.uk April 2005
PREFACE TO THE FOURTH EDITION In addition to complete updating, this edition of Principles of Molecular Virology contains a number of additions to the text and illustrations; for example, new information on topics such as SARS and bioterrorism. However, most changes have been made to the enclosed CD. In addition to complete reformatting, the content has been completely revised and we have been able to include for the first time a series of animations covering important topics such as capsid symmetry, virus replication and immune recognition and killing of virus-infected cells. There is also a new interactive self-assessment quiz for each chapter so you can judge for yourself your knowledge of virology. I would like to extend my thanks to the staff of Elsevier for their assistance during the preparation of the book. I am confident that readers will find this edition as useful as the previous ones. Alan J. Cann University of Leicester, UK alan.cann@leicester.ac.uk April 2005
PREFACE TO THE THIRD EDITION This edition of Principles of Moleclar Virology seeks to build on the success of the first and second editions.In addition to complete updating,numerous additions (and hopefully,enhancements)have been made to the text.These include new sec- tions on 'Viruses and Apoptosis'(Chapter 6)and 'Bacteriophages and Human Disease'(Chapter 7),the addition of learning objectives for each chapter and a new appendix describing key events in the history of virology (Appendix 3).However, probably the first change most readers will notice is a new format with the addi- tion of colour illustrations to enhance understanding of key points An exciting new development has been the inclusion of an electronic com- panion to the book in the form of the enclosed CD.In addition to interactive learning resources on the CD which complement each chapter,the 'Virology Online'section has been written to encourage readers with access to the internet to go beyond reading the text of the book to find more information online. I would like to extend my thanks to all of my academic colleagues who have helped with the preparation of this edition,but in particular I value the contribu- tion of the many people who have contacted me with suggestions and comments regarding the previous editions.I hope that readers of this edition will continue to do so.I would also like to thank the editorial staff of Academic Press for their support and assistance during the preparation of the book.Finally,I would like to thank my family for respecting the sign which has spent many hours on the door of my study,'I am working.Please don't come in'.It's OK now kids,I've taken the sign down. Alan J.Cann Department of Microbiology&Immunology University of Leicester Je2000
PREFACE TO THE THIRD EDITION This edition of Principles of Molecular Virology seeks to build on the success of the first and second editions. In addition to complete updating, numerous additions (and hopefully, enhancements) have been made to the text.These include new sections on ‘Viruses and Apoptosis’ (Chapter 6) and ‘Bacteriophages and Human Disease’ (Chapter 7), the addition of learning objectives for each chapter and a new appendix describing key events in the history of virology (Appendix 3). However, probably the first change most readers will notice is a new format with the addition of colour illustrations to enhance understanding of key points. An exciting new development has been the inclusion of an electronic companion to the book in the form of the enclosed CD. In addition to interactive learning resources on the CD which complement each chapter, the ‘Virology Online’ section has been written to encourage readers with access to the internet to go beyond reading the text of the book to find more information online. I would like to extend my thanks to all of my academic colleagues who have helped with the preparation of this edition, but in particular I value the contribution of the many people who have contacted me with suggestions and comments regarding the previous editions. I hope that readers of this edition will continue to do so. I would also like to thank the editorial staff of Academic Press for their support and assistance during the preparation of the book. Finally, I would like to thank my family for respecting the sign which has spent many hours on the door of my study, ‘I am working. Please don’t come in’. It’s OK now kids, I’ve taken the sign down. Alan J. Cann Department of Microbiology & Immunology University of Leicester June 2000
PREFACE TO THE SECOND )上DITION Much has changed since the first edition of Principles of Moleclar Virology was pub- lished in 1993,but the need for this book is now stronger than ever.This edition is completely revised and updated and contains many new figures and tables.As a result,it is somewhat longer,but not,I hope,so long that it loses sight of the orig- inal objective-to present the concerns of contemporary virology to students in a concise and digestible manner. Many people should be thanked for helping inspire this edition,but I will single out a few for particular mention.I am very grateful to all those who pro- vided feedback on the first edition and I have tried to include as many of their comments/requests as possible;in particular,coverage of the rapidly developing area of plant virology has been greatly expanded.I am also grateful to my teaching col- leagues in Leicester and eksewhere for their suggestions.Finally,the person who should perhaps receive most thanks is my long-suffering editor at Academic Press, Tessa Picknett. Alan J.Cann Department of Microbiology Immunology University of Leicester July 1996
PREFACE TO THE SECOND EDITION Much has changed since the first edition of Principles of Molecular Virology was published in 1993, but the need for this book is now stronger than ever. This edition is completely revised and updated and contains many new figures and tables. As a result, it is somewhat longer, but not, I hope, so long that it loses sight of the original objective—to present the concerns of contemporary virology to students in a concise and digestible manner. Many people should be thanked for helping inspire this edition, but I will single out a few for particular mention. I am very grateful to all those who provided feedback on the first edition and I have tried to include as many of their comments/requests as possible; in particular, coverage of the rapidly developing area of plant virology has been greatly expanded. I am also grateful to my teaching colleagues in Leicester and elsewhere for their suggestions. Finally, the person who should perhaps receive most thanks is my long-suffering editor at Academic Press, Tessa Picknett. Alan J. Cann Department of Microbiology & Immunology University of Leicester July 1996
PREFACE TO THE FIRST EDITION This book came about through my own need for a text to augment my under graduate lectures on virology.Not that there is a particular shortage of books on virology,but even during my own relatively short career,the subject has expanded so rapidly that most profesionals feel pressurized by the the task of keeping up with current trends,let alone the responsibility of initiating a new generation in such a rapidly changing discipline.Many excellent and recent texts exist that deal with the subject in a detailed and somewhat traditional manner;the second edition of Fields'Virology (Raven Press,1990),the third edition of Matthews'Plant Virology (Academic Press,1991)and,in a more general sense,the second edition of Molc ular Biology of the Cell (Garland Press,1989)immediately spring to mind.Unfor- tunately,these books have two major disadvantages for their use in teaching.First. the volume of material they contain is overwhelming for a student discovering the subject for the first time and who may be unable to sort out the information they uire from the mountain of detail they encounter.Second,in these times,few students can afford to purchase one of these tomes.Even persuading university libraries,whose budgets are under constant pressure,to purchase more than one or two copies is difficult and an inadequate solution in a time of expanding student numbers.Better then to reserve these texts for the reference purpose for which they are best suited and to introduce students to the subject in a gentler way. In discussion with many of my colleagues at this and other universities,it was clear that most felt there was a place for a text which would cover the current emphasis and concerns of virology.In these conversations,there was no doubt as to what was required.My contemporaries have no difficulty with the label 'molec- ular virology:but most when pressed would have difficulty in expressing a com- prehensive definition.Perhaps the best way to describe how I have approached the subject here is consider it as 'virology at a molecular level'or even better,'mole- cules and viruses:Having already damned the 2000-page reference source as unsuit-
PREFACE TO THE FIRST EDITION This book came about through my own need for a text to augment my undergraduate lectures on virology. Not that there is a particular shortage of books on virology, but even during my own relatively short career, the subject has expanded so rapidly that most professionals feel pressurized by the the task of keeping up with current trends, let alone the responsibility of initiating a new generation in such a rapidly changing discipline. Many excellent and recent texts exist that deal with the subject in a detailed and somewhat traditional manner; the second edition of Fields’Virology (Raven Press, 1990), the third edition of Matthews’ Plant Virology (Academic Press, 1991) and, in a more general sense, the second edition of Molecular Biology of the Cell (Garland Press, 1989) immediately spring to mind. Unfortunately, these books have two major disadvantages for their use in teaching. First, the volume of material they contain is overwhelming for a student discovering the subject for the first time and who may be unable to sort out the information they require from the mountain of detail they encounter. Second, in these times, few students can afford to purchase one of these tomes. Even persuading university libraries, whose budgets are under constant pressure, to purchase more than one or two copies is difficult and an inadequate solution in a time of expanding student numbers. Better then to reserve these texts for the reference purpose for which they are best suited and to introduce students to the subject in a gentler way. In discussion with many of my colleagues at this and other universities, it was clear that most felt there was a place for a text which would cover the current emphasis and concerns of virology. In these conversations, there was no doubt as to what was required. My contemporaries have no difficulty with the label ‘molecular virology,’ but most when pressed would have difficulty in expressing a comprehensive definition. Perhaps the best way to describe how I have approached the subject here is consider it as ‘virology at a molecular level’ or even better, ‘molecules and viruses.’ Having already damned the 2000-page reference source as unsuit-
Preface to the First Edition able for my purpose and yet such an all-embracing definition of'molecular virol- ogythe problem was therefore how to resolve these two apparently conficting issues.My chosen solution is to outline the principles of the subject with reference to specific examples chosen to illustrate the matter under discussion.The onus is therefore firmly on the reader to pursue particular matters on which he or she requires more information in more detailed 'reference texts'or in the immense volume of research publications appearing annually. I would like to have spent much more time discussing the history of virology in Chapter 1,a subject I find to be a fascinating as well as a valuable insight as to how we got to where we are today.In the event,it was only possible to provide a brief overview and to refer the reader to one of the many other texts which have been published on this subject-perhaps the one area of virology where an author's work does not become outdated in a short period.It is only my inten- tion to arm readers with the framework that makes it possible for them to achieve this task succesfully.Anyone who complains that this book does not spend suffi- cient time dealing with (or even mention)their pet area of interest has therefore missed the point. Todisarm the jargon (which I have avoided wherever possible)and unavoid- able technical terms,I have included a glossary as an appendix to the book.Terms shown in the text in bold print are defined in this glossary. Cliche it may be,but there are genuinely too many people to acknowledge for the creation of this book to make it possible to do this individually.It will have to suffice for me to thank all my colleagues in Leicester and elsewhere for helpful discussions;all the people who have helped and influenced my career over the years,and the undergraduates on whom I have field-tested the material,and for whom this book is intended. Alan J.Cann Microbiology Department University of Leicester October 1992
able for my purpose and yet such an all-embracing definition of ‘molecular virology,’ the problem was therefore how to resolve these two apparently conflicting issues. My chosen solution is to outline the principles of the subject with reference to specific examples chosen to illustrate the matter under discussion. The onus is therefore firmly on the reader to pursue particular matters on which he or she requires more information in more detailed ‘reference texts’ or in the immense volume of research publications appearing annually. I would like to have spent much more time discussing the history of virology in Chapter 1, a subject I find to be a fascinating as well as a valuable insight as to how we got to where we are today. In the event, it was only possible to provide a brief overview and to refer the reader to one of the many other texts which have been published on this subject—perhaps the one area of virology where an author’s work does not become outdated in a short period. It is only my intention to arm readers with the framework that makes it possible for them to achieve this task succesfully. Anyone who complains that this book does not spend suffi- cient time dealing with (or even mention) their pet area of interest has therefore missed the point. To disarm the jargon (which I have avoided wherever possible) and unavoidable technical terms, I have included a glossary as an appendix to the book.Terms shown in the text in bold print are defined in this glossary. Cliché it may be, but there are genuinely too many people to acknowledge for the creation of this book to make it possible to do this individually. It will have to suffice for me to thank all my colleagues in Leicester and elsewhere for helpful discussions; all the people who have helped and influenced my career over the years, and the undergraduates on whom I have field-tested the material, and for whom this book is intended. Alan J. Cann Microbiology Department University of Leicester October 1992 xiv Preface to the First Edition
THE PRINCIPLES OF MOLECULAR VIROLOGY CD Wherever theicon appears in the text,an accompanying learning resource can be found on the compact disk(CD)included with this book.Before starting,ensure that you have Macromedia FLASH Player installed on your machine.FLASH plays small,fast multimedia buttons,as well as interactive animations,flying logos,and graphics.This player is very small,takes only a short time to download,and is a great starting point for experiencing multimedia on the Web.To download the player for free,go to:http://www.macromedia.com/downloads/and select'Macromedia Flash Player'. To use the CD on a PC,put the disk into the CD-ROM drive,double-click on the My Computer icon,double-click on the CD-ROM icon and double-click on the Start.htm file.To use the CD on a Macintosh,put the disk into the CD- ROM drive,double-click on the CD-ROM icon on the desktop and double-click on the Start.htm file.If you need further help,click on the file 'README.txt'. The CD contains interactive learning resources which complement each chapter of the book.However,to gain the maximum benefit from the disk,you will need internet access.The resources in the'Virology Online'section have been selected to encourage you to move beyond the text of the book and find infor- mation about any topic you may wish to investigate.Not sure what any word or name in the text means?Type it into the search forms listed in 'Virology Online and you will be surprised how much information is available. However,readers should be aware that the quality and accuracy of information they may find on the internet varies greatly.All of the resources suggested on the CD are of the highest quality,although neither the author nor Academic Press can guarantee that they will remain freely available indefinitely.Information accessed through search engines is another matter-it is up to users to judge the quality of resources found in this way:
THE PRINCIPLES OF MOLECULAR VIROLOGY CD Wherever the icon appears in the text, an accompanying learning resource can be found on the compact disk (CD) included with this book. Before starting, ensure that you have Macromedia FLASH Player installed on your machine. FLASH plays small, fast multimedia buttons, as well as interactive animations, flying logos, and graphics. This player is very small, takes only a short time to download, and is a great starting point for experiencing multimedia on the Web. To download the player for free, go to: http://www.macromedia.com/downloads/ and select ‘Macromedia Flash Player’. To use the CD on a PC, put the disk into the CD-ROM drive, double-click on the My Computer icon, double-click on the CD-ROM icon and double-click on the Start.htm file. To use the CD on a Macintosh, put the disk into the CDROM drive, double-click on the CD-ROM icon on the desktop and double-click on the Start.htm file. If you need further help, click on the file ‘README.txt’. The CD contains interactive learning resources which complement each chapter of the book. However, to gain the maximum benefit from the disk, you will need internet access.The resources in the ‘Virology Online’ section have been selected to encourage you to move beyond the text of the book and find information about any topic you may wish to investigate. Not sure what any word or name in the text means? Type it into the search forms listed in ‘Virology Online’ and you will be surprised how much information is available. However, readers should be aware that the quality and accuracy of information they may find on the internet varies greatly. All of the resources suggested on the CD are of the highest quality, although neither the author nor Academic Press can guarantee that they will remain freely available indefinitely. Information accessed through search engines is another matter—it is up to users to judge the quality of resources found in this way: