VIROLOGY PRINCIPLES AND APPLICATIONS John B. Carter and Venetia A. Saunders
WILEY
-u rief Contents
Preface to Second Edition xix Preface to First Edition xxi Abbreviations Used in This Book xxiii Greek Letters Used in This Book xxvii Color Coding for Molecules xxix
Chapter 1
Viruses and Their Importance
Chapter 2
Methods Used in Virology
Chapter 3
Virus Structure
Chapter 4
Virus Transmission
Chapter 5
Attachment and Entry of Viruses into Cells
Chapter 6
Transcription, Translation, and Transport
Chapter 7
Virus Genome Replication
Chapter 8
Assembly and Exit of Virions from Cells
Chapter 9
Outcomes of Infection for the Host 101
Chapter 10
Classification and Nomenclature of Viruses
Chapter 11
Herpesviruses (and Other dsDNA Viruses)
Chapter 12
Parvoviruses (and Other ssDNA Viruses)
Chapter 13
Reoviruses (and Other dsRNA Viruses)
Chapter 14
Picornaviruses (and Other Plus-Strand RNA Viruses)
Chapter 15
Rhabdoviruses (and Other Minus-Strand RNA Viruses)
Chapter 16
Influenza Virus
Chapter 17
Retroviruses
Chapter 18
Human Immunodeficiency Viruses
Chapter 19
Hepadnaviruses (and Other Reverse-Transcribing DNA Viruses)
Chapter 20
Bacterial Viruses
Chapter 21
Origins and Evolution of Viruses
Chapter 22
Emerging Viruses
9
27 45 55 65
83 93 115 121 135 145 155 169
183 195 207 223
237 263
277 vii
Viii
BRIEF CONTENTS
Chapter 23
Viruses and Cancer
Chapter 24
Survival of Infectivity 301
Chapter 25
Virus Vaccines
Chapter 26
Anti-viral Drugs
Chapter 27
Prions
327
Virologists' Vocabulary Index 347
335
289
307 315 Pref Pref Ab~
Gre
Col
Cha
Chi
~wcontents
Preface to Second Edition xix Preface to First Edition xxi Abbreviations Used in This Book xxiii Greek Letters Used in This Book xxvii Color Coding for Molecules xxix
Chapter 1
Viruses and Their Importance 1.1 1.2
1.3
1.4
Chapter 2
Viruses Are Ubiquitous on Earth 2 Reasons for Studying Viruses 3 1.2.1 Some viruses cause disease 3 1.2.2 Some viruses are useful 3 1.2.3 Virus studies have contributed to knowledge 4 The Nature of Viruses 4 1.3.1 Viruses are small particles 4 1.3.2 Viruses have genes 5 1.3.3 Viruses are parasites 6 1.3.4 Some viruses are dependent on other viruses 6 1.3.5 Are viruses living or nonliving? 6 The Remainder of the Book 7
Methods Used in Virology 2.1 2.2 2.3 2.4
2.5
2.6 2.7
9
Introduction to Methods Used in Virology 11 Cultivation of Viruses 11 2.2.1 Animal cell culture 11 Isolation of Viruses 12 Centrifugation 14 2.4.1 Differential centrifugation 14 2.4.2 Density gradient centrifugation 14 Structural Investigations of Celts and Virions 15 2.5.1 Light microscopy 15 2.5.2 Electron microscopy 15 2.5.3 X-ray crystallography 16 Electrophoretic Techniques 16 Detection of Viruses and Virus Components 16 2.7.1 Detection of virions 16 2.7.2 Detection of infectivity using cell cultures 2.7.3 Detection of virus antigens 18 2.7.4 Detection of virus nucleic acids 18
Introduction to Virus Structure 28 Virus Genomes 28 3.2.1 Genome size 28 3.2.2 Secondary and tertiary structure 28 3.2.3 Modifications at the ends of virus genomes 29 3.2.4 Proteins non-covalently associated with virus genomes 3.2.5 Segmented genomes 33 3.2.6 Repeat sequences 33 Virus Proteins 33 Capsids 35 3.4.1 Capsids with helical symmetry 35 3.4.2 Capsids with icosahedral symmetry 36 3.4.3 Conical and rod-shaped capsids 40 Virion Membranes 40 3.5.1 Enveloped virions 41 3.5.2 Virions with internal membranes 42 3.5.3 Membrane lipids 42 Occlusion Bodies 42 Other Virion Components 43 3.7.1 Virus RNA in DNA viruses 43 3.7.2 Cell molecules in virions 43
32
Cl
45
Introduction to Virus Transmission 46 4.1.1 Transmission via vectors: general principles 46 Transmission of Plant Vi ruses 47 Transmission of Vertebrate Viruses 49 4.3.1 Non-vector transmission of vertebrate viruses 49 4.3.2 Vector transmission of vertebrate viruses 50 4.3.3 Virus survival in a new vertebrate host 51 Transmission of Invertebrate Viruses 51 Permissive Cells 52
Attachment and Entry of Viruses into Cells 5.1 5.2
Chi
27
Virus Transmission 4.1
24
Overview of Virus Replication Animal Viruses 57
56
55
c
p CONTENTS
5.3
Chapter 6
Transcription, Translation, and Transport 6.1 6.2 6.3
6.4
6.5 6.6
Chapter 7
7.3 7.4 7.5 7.6 7.7 7.8
83
Overview of Virus Genome Replication 84 Locations of Virus Genome Replication in Eukaryotic Cells 86 Initiation of Genome Replication 86 7.3.1 RNA and protein primers 86 Poly me rases 88 DNA Replication 88 Double-Stranded RNA Replication 90 Single-Stranded RNA Replication 90 Reverse Transcription 91
Assembly and Exit of Virions from Cells 8.1 8.2
65
Introduction to Transcription, Translation, and Transport Transcription of Virus Genomes 66 6.2.1 Modifications to the central dogma 68 Transcription in Eukaryotes 68 6.3.1 Promoters and enhancers 68 6.3.2 Transcription factors 70 6.3.3 Transcriptases 70 6.3.4 Capping transcripts 71 6.3.5 Polyadenylation of transcripts 72 6.3.6 Splicing transcripts 73 Translation in Eukaryotes 73 6.4.1 Initiation of translation 73 6.4.2 Translation from bicistronic mRNAs 75 6.4.3 Co- and post-translational modification of proteins 77 Transport of Molecules in Eukaryotic Cells 77 Transcription and Translation in Bacteria 80
Virus Genome Replication 7.1 7.2
Chapter 8
5.2.1 Cell receptors and co-receptors 57 5.2.2 Virus attachment sites 58 5.2.3 Attachment of virions to receptors 58 5.2.4 Entry of animal viruses into cells 58 5.2.5 Intracellular transport 60 5.2.6 Genome uncoating 63 Bacteriophages 63
93
Introduction to Assembly and Exit of Virions from Cells 94 Nucleocapsid Assembly 95 8.2.1 Helical viruses 95 8.2.2 Icosahedral viruses 95 8.2.3 Genome packaging 96 8.2.4 Assembly mechanisms 96
66
Xi
Xii
CONTENTS
8.3
8.4
Chapter 9
-
Chapte
98
Outcomes of Infection for the Host 101 9.1 9.2
9.3
9.4
Chapter 10
Formation of Virion Membranes 96 8.3.1 Budding through cell membranes 96 8.3.2 De novo synthesis of viral membranes Virion Exit From the Infected Cell 99
Introduction to Outcomes of Infection for the Host 103 Factors Affecting Outcomes of Infection 103 9.2.1 Innate immunity in vertebrates 103 9.2.2 Adaptive immunity in vertebrates 105 9.2.3 RNA silencing 108 9.2.4 Programmed cell death 108 Non-Productive Infections 109 9.3.1 Latent infections 109 9.3.2 Abortive infections 110 Productive Infections 110 9.4.1 Spread of infections within multicellular hosts 110 9.4.2 Disease 111
Chapt
Classification and Nomenclature of Viruses 115 10.1
History of Virus Classification and Nomenclature 116 10.1.1 International Committee on Taxonomy of Viruses 116 10.2 Modern Virus Classification and Nomenclature 116 10.2.1 Classification based on genome sequences 117 10.2.2 Nomenclature of viruses and taxonomic groups 117 10.3 Baltimore Classification of Viruses 119
Chapter 11
Herpesviruses (and Other dsDNA Viruses) 11.1 11.2
11.3 11.4 11.5
11.6 11.7
121
Introduction to Herpesviruses 122 The Human Herpesviruses 122 11.2.1 Herpes simplex viruses 1 and 2 122 11.2.2 Varicella-zoster virus 122 11.2.3 Epstein-Barr virus 122 11.2.4 Human cytomegalovirus 123 11.2.5 Human herpesvirus 6 123 11.2.6 Human herpesvirus 7 123 11.2.7 Kaposi's sarcoma-associated herpesvirus 123 The Herpesvirus Virion 123 HSV-1 Genome Organization 125 HSV-1 Replication 125 11.5.1 Attachment and entry 125 11.5.2 Transcription and translation 126 11.5.3 Genome replication 126 11.5.4 Assembly and exit of virions from the cell 128 11.5.5 Overview of HSV-1 replication 129 Latent Herpesvirus Infection 129 Other dsDNA Viruses 132
Chap
CONTENTS
Chapter 12
Parvoviruses (and Other ssDNA Viruses)
135
12.1 Introduction to Parvoviruses 136 12.2 Examples of Parvoviruses 136 12.2.1 Dependoviruses 136 12.2.2 Autonomous parvoviruses 137 12.3 Parvovirus Virion 137 12.3.1 Capsid 137 12.3.2 Genome 138 12.4 Parvovirus Replication 138 12.4.1 Attachment and entry 138 12.4.2 Single-stranded DNA to double-stranded DNA 139 12.4.3 Transcription and translation 139 12.4.4 DNA replication and virion assembly 140 12.4.5 Overview of parvovirus replication 140 12.4.6 Dependovirus replication 140 12.5 Other ssDNA Viruses 141
Chapter 13
Reoviruses (and Other dsRNA Viruses)
145
13.1 Introduction to Reoviruses 146 13.2 Rotavirus Virion 146 13.3 Rotavirus Replication 147 13.3.1 Attachment and entry 147 13.3.2 Early events 148 13.3.3 Late events 151 13.3.4 Overview of rotavirus replication 13.3.5 Rotavirus disease 152 13.4 Other dsRNA Viruses 153
Chapter 14
152
Picornaviruses (and Other Plus-Strand RNA Viruses)
155
14.1 Introduction to Picornaviruses 156 14.2 Some Important Picornaviruses 156 14.2.1 Hepatitis A virus 156 14.2.2 Poliovirus 156 14.2.3 Coxsackieviruses 156 14.2.4 Rhinoviruses 157 14.2.5 Foot and mouth disease virus 157 14.3 Picornavirus Virion 157 14.3.1 Capsid 158 14.3.2 Genome 159 14.4 Picornavirus Replication 160 14.4.1 Attachment 160 14.4.2 Entry 160 14.4.3 Translation and post-translational modifications 161 14.4.4 Transcription/ genome replication 161 14.4.5 Assembly and exit 164 14.4.6 Inhibition of host gene expression 164 14.4.7 Overview of picornavirus replication 164
Xiii
XiV
CONTENTS
14.5 Picornavirus Recombination 164 14.6 Picornavirus Experimental Systems 165 14.6.1 Reverse genetics 166 14.6.2 Cell-free synthesis of infectious virus 14.7 Other Plus-Strand RNA Viruses 167
Chapter 15
Rhabdoviruses (and Other Minus-Strand RNA Viruses)
166
169
Chi
15.1 Introduction to Rhabdoviruses 170 15.2 Some Important Rhabdoviruses 170 15.2.1 Rabies virus 170 15.2.2 Vesicular stomatitis virus 172 15.3 The Rhabdovirus Virion and Genome Organization 172 15.4 Rhabdovirus Replication 172 15.4.1 Attachment and entry 172 15.4.2 Transcription 174 15.4.3 Translation 175 15.4.4 Genome replication and secondary transcription 15.4.5 Assembly of virions and exit from the cell 177 15.4.6 Inhibition of host gene expression 177 15.4.7 Role of the nucleus 178 15.4.8 Overview of rhabdovirus replication 178 15.5 Other Minus-Strand RNA Viruses and Viruses with Ambisense Genomes 179 15.6 Reverse Genetics 180
Chapter 16
Influenza Virus
175
183
16.1 Introduction to Influenza Viruses 184 16.2 The Influenza Virion 184 16.3 Influenza A Virus Replication 186 16.3.1 Attachment and entry 186 16.3.2 RNA replication 187 16.3.3 Translation and transport of proteins 188 16.3.4 Virion assembly and release 189 16.3.5 Overview of influenza virus replication 190 16.4 Importance of Influenza Viruses 190 16.5 Reverse Genetics 192
Chapter 17
Retroviruses
195
17.1 Introduction to Retroviruses 196 17.2 Retrovirus Virion 196 17.3 Retrovirus Replication 196 17.3.1 Attachment and entry 196 17.3.2 Reverse transcription 198 17.3.3 Integration of the provirus 198 17.3.4 Transcription and genome replication 198 17.3.5 Translation and post-translational modifications
201
CONTENTS
17.3.6 Assembly and release of virions 202 17.3.7 Overview of retrovirus replication 203 17.4 Examples of Retroviruses 203 17.5 Retroviruses as Gene Vectors 205 17.6 Endogenous Retroviruses 205
Chapter 18
Human Immunodeficiency Viruses
207
18.1 18.2 18.3 18.4
Introduction to HIV 208 HIV Virion 208 HIV Genome 209 HIV-1 Replication 209 18.4.1 Attachment and entry 209 18.4.2 Reverse transcription and transport to the nucleus 18.4.3 Early gene expression 213 18.4.4 Late gene expression 214 18.4.5 Assembly and exit of virions 216 18.4.6 Overview of HIV-1 replication 217 18.5 HIV-1 Variability 217 18.5.1 Antigens 218 18.5.2 Host cell range 218 18.5.3 Resistance to drugs 219 18.6 Progression of HIV Infection 219 18.7 Prevention of HIV Transmission 220
Chapter 19
Hepadnaviruses (and Other Reverse-Transcribing DNA Viruses) 19.1 Introduction to Hepadnaviruses 224 19.2 Importance of HBV 224 19.3 HBV Virion 225 19.3.1 DNA 225 19.3.2 P (polymerase) protein 225 19.3.3 Capsid 225 19.3.4 Envelope 226 19.4 Non-Infectious Particles 226 19.5 Soluble Virus Protein 227 19.6 HBV Genome 227 19.7 HBV Genetic Groups 228 19.8 HBV Replication 228 19.8.1 Attachment 228 19.8.2 Entry 228 19.8.3 Transcription 229 19.8.4 Translation 231 19.8.5 Nucleocapsid assembly 231 19.8.6 Genome synthesis 232 19.8.7 Envelope acquisition and exit 232 19.8.8 Overview of HBV replication cycle 232 19.9 Prevention and Treatment of HBV Infection 235 19.10 Other Reverse-Transcrib ing DNA Viruses 236
21.1 Introduction to Origins and Evolution of Viruses 264 21 .2 Origins of Viruses 264 21.2.1 Molecular precursors of cellular organisms 264 21.2.2 Components of cells 265 21.2.3 Intracellular micro-organisms 265 21 .2.4 How did viruses originate? 265 21.3 Evolution of Viruses 266 21.3.1 Viruses from the past 266 21.3.2 Monitoring virus evolution 266 21 .3.3 Mechanisms of virus evolution 267 21.3.4 Evolution of new viruses 273 21.3.5 Co-evolution of viruses and their hosts 273
Chapter 22
Emerging Viruses
Chap
Chan
277
22.1 Introduction to Emerging Viruses 278 22.2 Viruses in New Host Species 278 22.2.1 Bunyaviruses 278 22.2.2 Paramyxoviruses 279 22.3 Viruses in New Areas 280 22.3.1 West Nile virus 280 22.3.2 Chikungunya virus 281 22.3.3 Bluetongue virus 282 22.4 Viruses in New Host Species and in New Areas 283 22.4.1 Filoviruses 283 22.4.2 Monkeypox virus 284 22.5 New viruses 285 22.5.1 SARS coronavirus 285 22.6 Recently Discovered Viruses 285 22.6.1 Human metapneumovirus 285
Introduction to Viruses and Cancer 290 Papillomavirus-Linked Cancers 291 Polyomavirus-Linked Cancers 291 Epstein-Barr Virus-Linked Cancers 292 Kaposi's Sarcoma 293 Adult T Cell Leukemia 294 Hepatocellular Carcinoma 294 Virus-Associated Cancers in Animals 294 Cell Lines Derived From Virus-Associated Cancers 294 How Do Viruses Cause Cancer? 295 23.10.1 "Deliberate" interference with control of cell activities 295 23.10.2 "Accidental" activation of cell genes 296 23.10.3 Retroviral oncogenes 296 23.10.4 Damage to immune defenses 297 23.10.5 Overview of cancer induction by viruses 297 23.11 Prevention of Virus-Induced Cancers 299
Chapter 24
Survival of Infectivity 24.1 24.2 24.3 24.4 24.5
Chapter 25
Preservation of Virus Infectivity 302 Destruction of Virus Infectivity 302 Inactivation Targets in Virions 302 Inactivation Kinetics 302 Agents that Inactivate Virus Infectivity 24.5.1 Physical agents 303 24.5.2 Chemical agents 304
Introduction to Virus Vaccines 308 Live Attenuated Virus Vaccines 308 Inactivated Virus Vaccines 310 Virion Subunit Vaccines 310 Live Recombinant Virus Vaccines 310 Mass-Production of Viruses for Vaccines Virus-Like Particles 312 Synthetic Peptide Vaccines 312 DNA Vaccines 313 Storage and Transport of Vaccines 313
311
XVii
~
lr
XViii
CONTENTS
Chapter 26
Anti-viral Drugs
315
26.1 Introduction to Anti-viral Drugs 316 26.2 Development of Anti-viral Drugs 316 26.2.1 Screening compounds for anti-viral activity 316 26.2.2 Rational design of anti-viral drugs 316 26.2.3 Safety of anti-viral drugs 317 26.3 Examples of Anti-viral Drugs 317 26.3.1 Nucleoside analogs 317 26.3.2 Non-nucleoside inhibitors of reverse transcription 26.3.3 HIV protease inhibitors 320 26.3.4 HIV attachment and fusion inhibitors 321 26.3.5 HIV integrase inhibitors 321 26.3.6 Influenza virus neuraminidase inhibitors 321 26.4 Drug Resistance 322 26.5 Anti-viral Drug Research 324
Chapter 27
Prions
327
27.1 Introduction to Prions 328 27.2 Transmissible Spongiform Encephalopathies 27.3 The Nature of Prions 328 27.3.1 Prion replication 330 27.4 Prion Diseases 330 27.4.1 Prion diseases in animals 330 27.4.2 Prion diseases in humans 331 27.5 Prion Strains 332 27.6 Prion Transmission 332 27.7 The Protein-Only Hypothesis 332 Virologists' Vocabulary Index 347