Tai Lieu Chat Luong VIROLOGY MOLECULAR BIOLOGY AND PATHOGENESIS This page intentionally left blank V ROLOGY MOLECULAR BIOLOGY AND PATHOGENESIS LEONARD C. NORKIN Department of Microbiology University of Massachusetts Amherst, Massachusetts ASM PRESS Washington, DC Address editorial correspondence to ASM Press, 1752 N St. NW, Washington, DC 20036-2904, USA Send orders to: ASM Press, P. Box 605, Herndon, VA 20172, USA Phone: (800) 546-2416 or (703) 661-1593 Fax: (703) 661-1501 E-mail: books@asmusa.org Online: http://estore.org Copyright © 2010 ASM Press American Society for Microbiology 1752 N St.
NW Washington, DC 20036-2904 Library of Congress Cataloging-in-Publication Data Norkin, Leonard C. Virology : molecular biology and pathogenesis / Leonard C. Includes bibliographical references and index. ISBN 978-1-55581-453-3 (hardcover : alk.
Molecular virology—Textbooks. Virus diseases— Pathogenesis—Textbooks. Virus Diseases—etiology.9′101—dc22 2009036895 10 9 8 7 6 5 4 3 2 1 All rights reserved Printed in Canada Cover and interior design: Susan Brown Schmidler Illustrations: Lineworks, Inc. Cover illustration: Structure and molecular organization of a Sindbis virus particle.
Sindbis virus is a member of the togavirus family of enveloped plus-strand RNA viruses. The surface features of the particle were determined by cryo-electron microscopy, which yielded hundreds of highly detailed, two-dimensional images, from which a three-dimensional image was generated using powerful computer programs. A cross-section through the particle, showing the envelope glycoproteins (blue), the lipid bilayer (green), the nucleocapsid (red), the mixed RNA-protein region (orange), and the genomic plus-strand RNA (magenta), is superimposed on the three-dimensional image. Protein structures were solved by X-ray crystallography, and then fitted into the cryo-EM structure.1 in the book for the complete image.
Zhang et al. I dedicate this book to my wife, Arline; my sons, Dave and Mike, and their wives, Mina and Debbie; and my grandchildren, Luke, Maya, and Theo. ‘‘Human subtlety will never devise an invention more beautiful, more simple or more direct than does Nature, because in her inventions, nothing is lacking and nothing is superfluous.’’ Leonardo da Vinci (1452–1519) This page intentionally left blank Contents Preface xix PART I Introduction 1 1 A Selective History on the Nature of Viruses 3 Introduction 3 The Early Years: Discoverers and Pioneers 4 The First Stirrings of the Molecular Era 7 The Phage Group 10 Phage Growth: Eclipse and Replication 11 Defining Viruses 15 Are Viruses Alive? 16 Origin of Viruses 17 The Modern Era of Animal Virology 17 2 Biosynthesis of Viruses: an Introduction to Virus Classification 20 T-Even Bacteriophages as a Model System 20 T-Even Phage Structure and Entry 22 Sequence of Phage Biosynthetic Events 24 Phage Protein Synthesis 24 RNA Metabolism in Infected Cells 25 Assembly of Progeny Phages 27 Packaging DNA within the Phage Particle 28 Unique Features of T-Even Phages 30 Modified Bases 30 Regulated Gene Expression 30 Phage Release: Lysozyme and the rII Region 32 Bacteriophage Lambda (λ): Lysogeny and Transduction 33 Some Final Comments on Bacteriophages 39 vii viii CONTENT S Introduction to the Animal Viruses 39 Animal Virus Structure 39 Entry of Animal Viruses 42 The Families of Animal Viruses: Principles of Classification 45 Viral Genetic Systems: the Baltimore Classification Scheme 45 3 Modes of Virus Infection and Disease 50 Introduction 50 Portals of Entry 50 Routes of Dissemination 54 Hematogenous and Neural Dissemination 54 The Placenta and the Fetus 60 Acute versus Persistent Infections 63 Acute Infections 64 Persistent Infections 66 Slow Infections 66 Chronic Infections 68 Latent Infections 74 Transmissible Spongiform Encephalopathies: Prions 76 4 Host Defenses and Viral Countermeasures 80 Introduction 80 Overview of Defenses 81 Physical Barriers against Infection 82 The Innate Immune System 82 Cytokines: the IFNs 84 Cytokines: TNF-α, Some Other Cytokines, and Inflammation 88 Macrophages, Neutrophils, NK Cells, and Antibody-Dependent Cellular Cytotoxicity 89 The Complement System 95 Viral Evasion of Innate Immunity 98 Evasion of IFNs 98 Evasion of Cytokines 100 Evasion of NK Cells and ADCC 101 Evasion of Complement 102 APOBEC3G and the HIV Vif Protein 103 The Adaptive Immune System 103 Antibodies and B Cells 104 Antibody Diversity 106 Viral Evasion of Antibodies 110 Cell-Mediated Immunity 113 Antigen Presentation by MHC Class I Molecules 119 Antigen Presentation by MHC Class II Molecules 119 The Rationale for MHC Restriction 121 Activation of Th Cells: Dendritic Cells and B Cells 124 Activation of B Cells 126 Activation of CTLs 128 Mechanism of Action of CTLs 129 CONTENTS ix T Cells and Antiviral Cytokines 131 Viral Evasion of Cell-Mediated Immunity 132 Inhibition of Antigen Presentation to CTLs 132 Inhibition of Antigen Presentation to Helper T Cells 134 Inhibition of Apoptosis 134 Immunological Memory 136 Self Tolerance 137 The Immune System in Disease 140 Immunopathology 140 Autoimmune Disease 141 PART II Virus Replication and Pathogenesis 147 RNA Viruses: Double Stranded 149 5 Reoviruses 149 Introduction 149 Structure, Binding, Entry, and Uncoating 150 Reovirus Binding and Entry into the Cell 150 Structure, Uncoating, and Entry into the Cytoplasm 154 The Reovirus Genome: Transcription and Translation 156 The Particle-Associated RNA Polymerase 156 The Segmented Reovirus Genome 158 Conversion of ISVPs to Cores 161 Replication and Encapsidation of the Reovirus Genome 165 Synthesis of Double-Stranded RNA 165 Assembly of Progeny Subviral Particles and Encapsidation of RNA Segments 166 Reoviruses and IFN 166 Primary versus Secondary Transcription 167 Final Virus Assembly 168 Pathogenesis 168 Orthoreoviruses 168 Rotaviruses 168 Coltiviruses 169 RNA Viruses: Single Stranded 171 6 Picornaviruses 171 Introduction 171 Structure, Binding, and Entry 172 Picornavirus Structure 172 Rhinovirus Receptor and Binding: the Canyon Hypothesis 173 The Poliovirus Receptor 177 Receptors for Coxsackieviruses and Other Enteroviruses 179 Receptors for FMDVs 180 Poliovirus and Rhinovirus Entry: Some General Points 181 Poliovirus Entry 181 x CONTENT S Human Rhinovirus Entry 183 Poliovirus and Rhinovirus Entry: Why the Differences? 184 Translation 184 Translation: Part I 184 Translation: a Digression 187 The RNA Phages 187 Picornaviruses versus RNA Phages: Why the Differences? 191 Translation: Part II 192 Transcription and Genome Replication 194 Assembly and Maturation 198 Medical Aspects 200 Poliovirus 200 Rhinoviruses: the Common Cold 203 Coxsackievirus and Echovirus 205 Viral Hepatitis: Hepatitis A 205 7 Flaviviruses 207 Introduction 207 Structure and Entry 208 Replication 209 Assembly and Release 209 Historic Interlude: Identification of Hepatitis C Virus 212 West Nile Virus: an Emerging Virus 213 Epidemiology and Pathogenesis 214 General Principles of Arthropod Transmission 214 Infection, Dissemination, and Determinants of Pathogenesis 215 Hemorrhagic Fever Viruses: Yellow Fever and Dengue Viruses 217 Encephalitis Viruses: Japanese Encephalitis, St. Louis Encephalitis, and West Nile Viruses 218 Japanese Encephalitis and St.
Louis Encephalitis Viruses 218 West Nile Virus 220 Hepatitis C Virus 220 8 Togaviruses 224 Introduction 224 Structure and Entry 225 Transcription, Translation, and Genome Replication 228 Assembly and Maturation 231 Epidemiology and Pathogenesis 232 Alphaviruses That Cause Encephalitis: Eastern, Western, and Venezuelan Equine Encephalitis Viruses 232 Alphaviruses That Cause Arthritis: Chikungunya, Ross River, and Sindbis Viruses 232 Rubella Virus 232 CONTENTS xi 9 Coronaviruses 235 Introduction 235 Structure 236 Entry 237 Genome Organization and Expression 238 Coronavirus mRNAs and Their Translation 238 Coronavirus Transcription 243 Coronavirus Recombination 247 Coronavirus Reverse Genetics 248 Assembly and Release 250 Medical Aspects 251 SARS 252 10 Rhabdoviruses 261 Introduction 261 Structure 262 Entry 263 Genome Organization, Expression, and Replication 264 The General Transcriptional Strategy of Viruses That Contain Negative-Sense RNA Genomes 264 Gene Organization and Transcription 264 Replication 267 Assembly and Release 268 Medical Aspects 269 Cytopathic Effects 269 VSV 270 Rabies Virus 270 11 Paramyxoviruses 273 Introduction 273 Structure 274 Entry 276 Syncytium Formation 279 Genome Organization, Expression, and Replication 279 Genome Organization and Transcription 279 Replication 281 Assembly and Release 282 Medical Aspects 282 Measles 282 Clinical Conditions 282 SSPE 285 Where Did Measles Come from? 288 Measles Vaccine 289 Mumps 290 Parainfluenza Viruses 290 Respiratory Syncytial Virus 291 xii CONTENT S HMPV 292 Hendra, Nipah, and Menangle Viruses 294 CDV 295 12 Orthomyxoviruses 296 Introduction 296 Structure 298 Entry 299 Endocytosis and Intracellular Trafficking of Influenza Virus-Containing Endosomes 300 Viral Membrane Fusion: the HA Protein 302 Release of the Genome from the Envelope: the M2 Protein 307 Transport of vRNPs to the Cell Nucleus 308 Genome Organization, Transcription, and Replication 311 Genome Organization and Transcription 311 Why Does Influenza Virus Transcription Really Occur in the Nucleus? 317 Replication 317 The NS1 and PB1-F2 Proteins 318 Assembly and Release 322 Assembly of vRNPs 322 Two Issues Regarding Intracellular Targeting of Viral Components 322 Transport of vRNPs from Nucleus to Cytoplasm 322 Apical Targeting of Virus Components and Final Virus Assembly 323 Encapsidating Eight Distinct Genomic Segments 325 Release: the Influenza Virus NA Protein 325 Medical Aspects 325 Pathology and Clinical Syndromes 325 The Flu Pandemic of 1918 326 Origin of Epidemic and Pandemic Strains: Antigenic Drift and Antigenic Shift 328 Virulence of the 1918 Pandemic Influenza Virus: Opening Pandora’s Box 333 Influenza Drugs and Vaccines 336 Avian Influenza and Humans 337 Preparedness for an Outbreak of Avian Influenza 341 13 Miscellaneous RNA Viruses 346 Introduction 346 Arenaviruses 347 Lassa Fever Virus: an Early Emerging Virus 348 LCMV and Immunopathology 348 The Ambisense Arenavirus Genome 349 Bunyaviruses 350 Sin Nombre and Hantaan Viruses 351 The Tripartite Bunyavirus Genome 351 Bornaviruses 352 BDV and Human Neuropsychiatric Disease 352 Bornavirus Genomes and Their Nuclear Transcription and Replication 354 Caliciviruses 355 Norwalk Virus (Norovirus) 355 Calicivirus Replication 356 Astroviruses 356 CONTENTS xiii Hepatitis E-Like Viruses 357 Filoviruses 358 Structure and Replication 358 Marburg and Ebola Viruses 358 Is Ebola Virus the “Andromeda Strain?