Principles of Virology, the leading virology textbook in use, is an extremely valuable and highly informative presentation of virology at the interface of modern cell biology and immunology. This text utilizes a uniquely rational approach by highlighting common principles and processes across all viruses. Using a set of representative viruses to illustrate the breadth of viral complexity, students are able to under-stand viral reproduction and pathogenesis and are equipped with the necessary tools for future encounters with new or understudied viruses.
This fifth edition was updated to keep pace with the ever-changing field of virology. In addition to the beloved full-color illustrations, video interviews with leading scientists, movies, and links to exciting blogposts on relevant topics, this edition includes study questions and active learning puzzles in each chapter, as well as short descriptions regarding the key messages of references of special interest.
Volume I: Molecular Biology focuses on the molecular processes of viral reproduction, from entry through release. Volume II: Pathogenesis and Control addresses the interplay between viruses and their host organisms, on both the micro- and macroscale, including chapters on public health, the immune response, vaccines and other antiviral strategies, viral evolution, and a brand new chapter on the therapeutic uses of viruses. These two volumes can be used for separate courses or together in a single course. Each includes a unique appendix, glossary, and links to internet resources.
Principles of Virology, Fifth Edition, is ideal for teaching the strategies by which all viruses reproduce, spread within a host, and are maintained within populations. This edition carefully reflects the results of extensive vetting and feedback received from course instructors and students, making this renowned textbook even more appropriate for undergraduate and graduate courses in virology, microbiology, and infectious diseases.
, Vincent R. Racaniello
, Glenn F. Rall
, Theodora Hatziioannou
, Anna Marie Skalka
American Society for Microbiology
Country of Publication:
Publication Date: 16 October 2020
Professional and scholarly
Preface xvii Acknowledgments xxi About the Authors xxiii Key of Repetitive Elements xxv Part I The Science of Virology 1 1 Foundations 2 Luria's Credo 3 Viruses Defined 3 Why We Study Viruses 3 Viruses Are Everywhere 3 Viruses Infect All Living Things 4 Viruses Can Cause Human Disease 5 Viruses Can Be Beneficial 5 Viruses R Us 6 Viruses Can Cross Species Boundaries 6 Viruses Are Unique Tools To Study Biology 6 Virus Prehistory 7 Viral Infections in Antiquity 7 The First Vaccines 8 Microorganisms as Pathogenic Agents 9 Discovery of Viruses 11 The Defining Properties of Viruses 13 The Structural Simplicity of Virus Particles 13 The Intracellular Parasitism of Viruses 13 Cataloging Animal Viruses 18 The Classical System 18 Classification by Genome Type: the Baltimore System 19 A Common Strategy for Viral Propagation 21 Perspectives 21 References 24 Study Questions 24 2 The Infectious Cycle 26 Introduction 27 The Infectious Cycle 27 The Cell 27 Entering Cells 28 Viral RNA Synthesis 29 Viral Protein Synthesis 29 Viral Genome Replication 29 Assembly of Progeny Virus Particles 29 Viral Pathogenesis 29 Overcoming Host Defenses 30 Cultivation of Viruses 30 Cell Culture 30 Embryonated Eggs 35 Laboratory Animals 35 Assay of Viruses 35 Measurement of Infectious Units 35 Efficiency of Plating 38 Measurement of Virus Particles 40 Viral Reproduction: The Burst Concept 49 The One-Step Growth Cycle 49 One-Step Growth Analysis: a Valuable Tool for Studying Animal Viruses 52 Global Analysis 53 DNA Microarrays 54 Mass Spectrometry 56 Protein-Protein Interactions 56 Single-Cell Virology 56 Perspectives 58 References 59 Study Questions 60 Part II Molecular Biology 61 3 Genomes and Genetics 62 Introduction 63 Genome Principles and the Baltimore System 63 Structure and Complexity of Viral Genomes 63 DNA Genomes 64 RNA Genomes 65 What Do Viral Genomes Look Like? 68 Coding Strategies 69 What Can Viral Sequences Tell Us? 69 The Big and Small of Viral Genomes: Does Size Matter? 71 The Origin of Viral Genomes 73 Genetic Analysis of Viruses 74 Classical Genetic Methods 75 Engineering Mutations into Viral Genomes 77 Engineering Viral Genomes: Viral Vectors 83 Perspectives 87 References 87 Study Questions 88 4 Structure 90 Introduction 91 Functions of the Virion 91 Nomenclature 92 Methods for Studying Virus Structure 92 Building a Protective Coat 95 Helical Structures 96 Capsids with Icosahedral Symmetry 99 Other Capsid Architectures 111 Packaging the Nucleic Acid Genome 112 Direct Contact of the Genome with a Protein Shell 112 Packaging by Specialized Viral Proteins 113 Packaging by Cellular Proteins 113 Viruses with Envelopes 115 Viral Envelope Components 115 Simple Enveloped Viruses: Direct Contact of External Proteins with the Capsid or Nucleocapsid 117 Enveloped Viruses with an Additional Protein Layer 118 Large Viruses with Multiple Structure Elements 119 Particles with Helical or Icosahedral Parts 120 Alternative Architectures 123 Other Components of Virions 125 Enzymes 125 Other Viral Proteins 125 Cellular Macromolecules 126 Mechanical Properties of Virus Particles 126 Investigation of Mechanical Properties of Virus Particles 126 Stabilization and Destabilization of Virus Particles 128 Perspectives 128 References 129 Study Questions 130 5 Attachment and Entry 132 Introduction 133 Attachment of Virus Particles to Cells 133 General Principles 133 Identification of Receptors for Virus Particles 135 Virus-Receptor Interactions 137 Entry into Cells 142 Virus-induced Signaling via Cell Receptors 142 Routes of Entry 143 Membrane Fusion 145 Intracellular Trafficking and Uncoating 154 Movement of Viral and Subviral Particles within Cells 154 Uncoating of Enveloped Virus Particles 155 Uncoating of Nonenveloped Viruses 155 Import of Viral Genomes into the Nucleus 159 The Nuclear Pore Complex 159 Nuclear Localization Signals 159 Nuclear Import of RNA Genomes 161 Nuclear Import of DNA Genomes 162 Import of Retroviral Genomes 162 Perspectives 164 References 165 Study Questions 166 6 Synthesis of RNA from RNA Templates 168 Introduction 169 The Nature of the RNA Template 169 Secondary Structures in Viral RNA 169 Naked or Nucleocapsid RNA 170 The RNA Synthesis Machinery 171 Identification of RNA-Dependent RNA Polymerases 171 Three-Dimensional Structures of RNA-Dependent RNA Polymerases 173 Mechanisms of RNA Synthesis 176 Initiation 176 Capping 179 Elongation 179 Functions of Additional Polymerase Domains 181 RNA Polymerase Oligomerization 181 Template Specificity 182 Unwinding the RNA Template 182 Role of Cellular Proteins 183 Paradigms for Viral RNA Synthesis 183 (+) Strand RNA 184 Synthesis of Nested Subgenomic mRNAs 184 ( ) Strand RNA 185 Ambisense RNA 189 Double-Stranded RNA 189 Unique Mechanisms of mRNA and Genome Synthesis of Hepatitis Delta Virus 190 Do Ribosomes and RNA Polymerases Collide? 192 Origins of Diversity in RNA Virus Genomes 193 Misincorporation of Nucleotides 193 Segment Reassortment and RNA Recombination 193 RNA Editing 194 Perspectives 195 References 196 Study Questions 197 7 Synthesis of RNA from DNA Templates 198 Introduction 199 Properties of Cellular RNA Polymerases That Transcribe Viral DNA 199 Some Viral Genomes Must Be Converted to Templates Suitable for Transcription 200 Transcription by RNA Polymerase II 201 Regulation of RNA Polymerase II Transcription 203 Common Properties of Proteins That Regulate Transcription 206 Transcription of Viral DNA Templates by the Cellular Machinery Alone 208 Viral Proteins That Govern Transcription of DNA Templates 209 Patterns of Regulation 209 The Human Immunodeficiency Virus Type 1 Tat Protein Autoregulates Transcription 211 The Transcriptional Cascades of DNA Viruses 217 Entry into One of Two Alternative Transcriptional Programs 226 Transcription of Viral Genes by RNA Polymerase III 230 The VA-RNA I Promoter 231 Inhibition of the Cellular Transcriptional Machinery 232 Unusual Functions of Cellular Transcription Components in Virus-Infected Cells 233 Viral DNA-Dependent RNA Polymerases 233 Perspectives 234 References 235 Study Questions 236 8 Processing 238 Introduction 239 Covalent Modification during Viral Pre-mRNA Processing 240 Capping the 5' Ends of Viral mRNA 240 Synthesis of 3' Poly(A) Segments of Viral mRNA 243 Internal Methylation of Adenosine Residues 245 Splicing of Viral Pre-mRNA 246 Regulated Processing of Viral Pre-mRNA 249 Editing of Viral mRNAs 255 Export of RNAs from the Nucleus 257 The Cellular Export Machinery 257 Export of Viral mRNA 258 Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins 262 Temporal Control of Viral Gene Expression 262 Viral Proteins Can Inhibit Cellular mRNA Production 264 Regulation of Turnover of Viral and Cellular mRNAs in the Cytoplasm 266 Intrinsic Turnover 266 Regulation of mRNA Stability by Viral Proteins 267 mRNA Stabilization Can Facilitate Transformation 267 Nonsense-Mediated mRNA Decay 267 Noncoding RNAs 271 Small Interfering RNAs and Micro-RNAs 271 Long Noncoding RNAs 276 Circular RNAs 278 Perspectives 278 References 279 Study Questions 281 9 Replication of DNA Genomes 282 Introduction 283 DNA Synthesis by the Cellular Replication Machinery 284 Eukaryotic Replicons 284 Cellular Replication Proteins 287 Mechanisms of Viral DNA Synthesis 287 Lessons from Simian Virus 40 288 Replication of Other Viral DNA Genomes 290 Properties of Viral Replication Origins 294 Recognition of Viral Replication Origins 296 Viral DNA Synthesis Machines 301 Resolution and Processing of Viral Replication Products 301 Exponential Accumulation of Viral Genomes 302 Viral Proteins Can Induce Synthesis of Cellular Replication Proteins 303 Synthesis of Viral Replication Machines and Accessory Enzymes 304 Viral DNA Replication Independent of Cellular Proteins 304 Delayed Synthesis of Structural Proteins Prevents Premature Packaging of DNA Templates 305 Inhibition of Cellular DNA Synthesis 305 Synthesis of Viral DNA in Specialized Intracellular Compartments 305 Limited Replication of Viral DNA Genomes 308 Integrated Parvoviral DNA Can Be Replicated as Part of the Cellular Genome 308 Different Viral Origins Regulate Replication of Epstein-Barr Virus 310 Limited and Amplifying Replication from a Single Origin: the Papillomaviruses 313 Origins of Genetic Diversity in DNA Viruses 315 Fidelity of Replication by Viral DNA Polymerases 315 Modulation of the DNA Damage Response 316 Recombination of Viral Genomes 318 Perspectives 321 References 321 Study Questions 323 10 Reverse Transcription and Integration 324 Retroviral Reverse Transcription 325 Discovery 325 Impact 325 The Process of Reverse Transcription 326 General Properties and Structure of Retroviral Reverse Transcriptases 334 Other Examples of Reverse Transcription 337 Retroviral DNA Integration 340 The Pathway of Integration: Integrase-Catalyzed Steps 341 Integrase Structure and Mechanism 347 Hepadnaviral Reverse Transcription 350 A DNA Virus with Reverse Transcriptase 350 The Process of Hepadnaviral Reverse Transcription 352 Perspectives 358 References 359 Study Questions 360 11 Protein Synthesis 362 Introduction 363 Mechanisms of Eukaryotic Protein Synthesis 363 General Structure of Eukaryotic mRNA 363 The Translation Machinery 364 Initiation 365 Elongation and Termination 375 The Diversity of Viral Translation Strategies 378 Polyprotein Synthesis 378 Leaky Scanning 378 Reinitiation 381 StopGo Translation 382 Suppression of Termination 382 Ribosomal Frameshifting 383 Bicistronic mRNAs 384 Regulation of Translation during Viral Infection 385 Inhibition of Translation Initiation after Viral Infection 385 Regulation of eIF4F 389 Regulation of Poly(A)-Binding Protein Activity 392 Regulation of eIF3 392 Interfering with RNA 392 Stress-Associated RNA Granules 393 Perspectives 395 References 396 Study Questions 397 12 Intracellular Trafficking 398 Introduction 399 Assembly within the Nucleus 400 Import of Viral Proteins for Assembly 401 Assembly at the Plasma Membrane 403 Transport of Viral Membrane Proteins to the Plasma Membrane 404 Sorting of Viral Proteins in Polarized Cells 419 Disruption of the Secretory Pathway in Virus-Infected Cells 421 Signal Sequence-Independent Transport of Viral Proteins to the Plasma Membrane 422 Interactions with Internal Cellular Membranes 426 Localization of Viral Proteins to Compartments of the Secretory Pathway 426 Localization of Viral Proteins to the Nuclear Membrane 426 Transport of Viral Genomes to Assembly Sites 427 Transport of Genomic and Pregenomic RNA from the Nucleus to the Cytoplasm 427 Transport of Genomes from the Cytoplasm to the Plasma Membrane 429 Perspectives 430 References 431 Study Questions 432 13 Assembly, Release, and Maturation 434 Introduction 435 Methods of Studying Virus Assembly and Egress 435 Structural Studies of Virus Particles 436 Visualization of Assembly and Exit by Microscopy 436 Biochemical and Genetic Analyses of Assembly Intermediates 436 Methods Based on Recombinant DNA Technology 439 Assembly of Protein Shells 439 Formation of Structural Units 439 Capsid and Nucleocapsid Assembly 441 Self-Assembly and Assisted Assembly Reactions 445 Selective Packaging of the Viral Genome and Other Components of Virus Particles 447 Concerted or Sequential Assembly 447 Recognition and Packaging of the Nucleic Acid Genome 448 Incorporation of Enzymes and Other Nonstructural Proteins 458 Acquisition of an Envelope 459 Sequential Assembly of Internal Components and Budding from a Cellular Membrane 459 Coordination of the Assembly of Internal Structures with Acquisition of the Envelope 460 Release of Virus Particles 460 Assembly and Budding at the Plasma Membrane 461 Assembly at Internal Membranes: the Problem of Exocytosis 464 Release of Nonenveloped Virus Particles 470 Maturation of Progeny Virus Particles 470 Proteolytic Processing of Structural Proteins 470 Other Maturation Reactions 474 Cell-to-Cell Spread 475 Perspectives 479 References 479 Study Questions 481 14 The Infected Cell 482 Introduction 483 Signal Transduction 483 Signaling Pathways 483 Signaling in Virus-Infected Cells 485 Gene Expression 489 Inhibition of Cellular Gene Expression 489 Differential Regulation of Cellular Gene Expression 492 Metabolism 496 Methods To Study Metabolism 496 Glucose Metabolism 497 The Citric Acid Cycle 501 Electron Transport and Oxidative Phosphorylation 502 Lipid Metabolism 504 Remodeling of Cellular Organelles 507 The Nucleus 509 The Cytoplasm 511 Perspectives 516 References 518 Study Questions 519 Appendix Structure, Genome Organization, and Infectious Cycles of Viruses Featured in This Book 521 Glossary 557 Index 563
Jane Flint is Professor Emerita of Molecular Biology at Princeton University. Dr. Flint's research focused on investigation of the mechanisms by which viral gene products modulate host pathways and antiviral defenses to allow efficient reproduction in normal human cells of adenoviruses, viruses that are used in such therapeutic applications as gene transfer and cancer treatment. Vincent R. Racaniello is Higgins Professor of Microbiology & Immunology at Columbia University Vagelos College of Physicians & Surgeons. Dr. Racaniello has been studying viruses for over 40 years, including polio- virus, rhinovirus, enteroviruses, hepatitis C virus, and Zika virus. He blogs about virus-es at virology.ws and is host of This Week in Virology. Glenn F. Rall is a Professor and the Chief Academic Officer at the Fox Chase Cancer Center, and is an Adjunct Professor in the Microbiology and Immunology departments at the University of Pennsylvania, as well as Thomas Jefferson, Drexel, and Temple Universities. Dr. Rall studies viral infections of the brain and the immune responses to those infections, with the goal of defining how viruses contribute to disease. Theodora Hatziioannou is a Research Associate Professor at Rockefeller University and is actively involved in teaching programs at Albert Einstein College of Medicine. Dr. Hatziioannou has worked on multiple viruses with a focus on retroviruses and the molecular mechanisms that govern virus tropism and on the improvement of animal models for human disease. Anna Marie Skalka is a Professor Emerita and former Senior Vice President for Basic Research at the Fox Chase Cancer Center. Dr. Skalka is internationally recognized for her contributions to the understanding of the biochemical mechanisms by which retroviruses replicate and insert their genetic material into the host genome, as well as her research into other molecular aspects of retrovirus biology.