Principles of Virology: Multi-Volume (5th Edition)

Description

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.

Table of Contents

1. Volume 1
2. Preface
3. Acknowledgments
4. About the Authors
5. PART I: The Science of Virology
6. 1 Foundations
   1. Luria’s Credo
   2. Viruses Defined
   3. Why We Study Viruses
   4. Viruses Are Everywhere
   5. Viruses Infect All Living Things
   6. Viruses Can Cause Human Disease
   7. Viruses Can Be Beneficial
   8. Viruses “R” Us
   9. Viruses Can Cross Species Boundaries
   10. Viruses Are Unique Tools To Study Biology
   11. Virus Prehistory
   12. Viral Infections in Antiquity
   13. The First Vaccines Microorganisms as Pathogenic Agents
   14. Discovery of Viruses
   15. The Defining Properties of Viruses
   16. The Structural Simplicity of Virus Particles
   17. The Intracellular Parasitism of Viruses
   18. Cataloging Animal Viruses
   19. The Classical System
   20. Classification by Genome Type: the  Baltimore System
   21. A Common Strategy for Viral Propagation
   22. Perspectives
   23. References
   24. Study Questions
7. 2 The Infectious Cycle
   1. Introduction
   2. The Infectious Cycle
   3. The Cell
   4. Entering Cells
   5. Viral RNA Synthesis
   6. Viral Protein Synthesis
   7. Viral Genome Replication
   8. Assembly of Progeny Virus Particles
   9. Viral Pathogenesis
   10. Overcoming Host Defenses
   11. Cultivation of Viruses
   12. Cell Culture
   13. Embryonated Eggs
   14. Laboratory Animals
   15. Assay of Viruses
   16. Measurement of Infectious Units
   17. Efficiency of Plating
   18. Measurement of Virus Particles
   19. Viral Reproduction: the Burst Concept
   20. The One-Step Growth Cycle
   21. One-Step Growth Analysis: a Valuable Tool for Studying Animal Viruses
   22. Global Analysis
   23. DNA Microarrays
   24. Mass Spectrometry
   25. Protein-Protein Interactions
   26. Single-Cell Virology
   27. Perspectives
   28. References
   29. Study Questions
8. PART II: Molecular Biology
9. 3 Genomes and Genetics
   1. Introduction
   2. Genome Principles and the Baltimore System
   3. Structure and Complexity of Viral Genomes
   4. DNA Genomes
   5. RNA Genomes
   6. What Do Viral Genomes Look Like?
   7. Coding Strategies
   8. What Can Viral Sequences Tell Us?
   9. The “Big and Small” of Viral Genomes: Does Size Matter?
   10. The Origin of Viral Genomes
   11. Genetic Analysis of Viruses
   12. Classical Genetic Methods
   13. Engineering Mutations into Viral Genomes
   14. Engineering Viral Genomes: Viral Vectors
   15. Perspectives
   16. References
   17. Study Questions
10. 4 Structure
    1. Introduction
    2. Functions of the Virion
    3. Nomenclature
    4. Methods for Studying Virus Structure
    5. Building a Protective Coat
    6. Helical Structures
    7. Capsids with Icosahedral Symmetry
    8. Other Capsid Architectures
    9. Packaging the Nucleic Acid Genome
    10. Direct Contact of the Genome with a Protein Shell
    11. Packaging by Specialized Viral Proteins
    12. Packaging by Cellular Proteins
    13. Viruses with Envelopes
    14. Viral Envelope Components
    15. Simple Enveloped Viruses: Direct Contact of External Proteins with the Capsid or Nucleocapsid
    16. Enveloped Viruses with an Additional Protein Layer
    17. Large Viruses with Multiple
    18. Structural Elements Particles with Helical or Icosahedral Parts Alternative Architectures
    19. Other Components of Virions
    20. Enzymes
    21. Other Viral Proteins
    22. Cellular Macromolecules
    23. Mechanical Properties of Virus Particles
    24. Investigation of Mechanical Properties of Virus Particles
    25. Stabilization and Destabilization of Virus Particles
    26. Perspectives
    27. References
    28. Study Questions
11. 5 Attachment and Entry
    1. Introduction
    2. Attachment of Virus Particles to Cells
    3. General Principles
    4. Identification of Receptors for Virus Particles
    5. Virus-Receptor Interactions
    6. Entry into Cells
    7. Virus-induced Signaling via Cell Receptors
    8. Routes of entry
    9. Membrane Fusion
    10. Intracellular Trafficking and Uncoating
    11. Movement of Viral and Subviral Particles within Cells
    12. Uncoating of enveloped viruses
    13. Uncoating of non-enveloped viruses
    14. Import of Viral Genomes into the Nucleus
    15. The Nuclear Pore Complex
    16. Nuclear Localization Signals
    17. Import of RNA Genomes
    18. Import of DNA Genomes
    19. Import of Retroviral Genomes
    20. Perspectives
    21. References
    22. Study Questions
12. 6 Synthesis of RNA from RNA Templates
    1. Introduction
    2. The Nature of the RNA Template
    3. Secondary Structures in Viral RNA
    4. Naked or Nucleocapsid RNA
    5. The RNA Synthesis Machinery
    6. Identification of RNA-Dependent RNA Polymerases
    7. Three-Dimensional Structures of RNA-Dependent RNA Polymerases
    8. Mechanisms of RNA Synthesis
    9. Initiation
    10. Capping
    11. Elongation
    12. Functions of Additional Polymerase Domains
    13. RNA polymerase Oligomerization
    14. Template Specificity
    15. Unwinding the RNA Template
    16. Role of Cellular Proteins
    17. Paradigms for Viral RNA Synthesis
    18. (+) Strand RNA
    19. Synthesis of Nested Subgenomic mRNAs
    20. (−) Strand RNA
    21. Ambisense RNA
    22. Double-Stranded RNA
    23. Unique Mechanisms of mRNA and Genome Synthesis of Hepatitis Delta Satellite Virus
    24. Do Ribosomes and RNA Polymerases Collide?
    25. Origins of Diversity in RNA Virus Genomes
    26. Misincorporation of Nucleotides
    27. Segment Reassortment and RNA Recombination
    28. RNA Editing
    29. Perspectives
    30. References
    31. Study Questions
13. 7 Synthesis of RNA from DNA Templates
    1. Introduction
    2. Properties of Cellular RNA Polymerases That Transcribe Viral DNA
    3. Some Viral Genomes Must Be Converted to Templates Suitable for Transcription
    4. Transcription by RNA Polymerase II
    5. Regulation of RNA Polymerase II Transcription
    6. Common Properties of Proteins That Regulate Transcription
    7. Transcription of Viral DNA Templates by the Cellular Machinery Alone
    8. Viral Proteins That Govern Transcription of DNA Templates
    9. Patterns of Regulation
    10. The Human Immunodeficiency Virus Type 1 Tat Protein Autoregulates Transcription
    11. The Transcriptional Cascades of DNA Viruses
    12. Entry into One of Two Alternative Transcriptional Programs
    13. Transcription of Viral Genes by RNA Polymerase III
    14. The VA-RNA I Promoter
    15. Inhibition of the Cellular Transcriptional Machinery
    16. Unusual Functions of Cellular Transcription Components in Virus-Infected Cells
    17. Viral DNA-Dependent RNA Polymerases
    18. Perspectives
    19. References
    20. Study Questions
    21. 8 Processing
    22. Introduction
    23. Covalent Modification during Viral Pre-mRNA Processing
    24. Capping the 5′ Ends of Viral mRNA
    25. Synthesis of 3′ Poly(A) Segments of Viral mRNA
    26. Internal Methylation of Adenosine Residues
    27. Splicing of Viral Pre-mRNA
    28. Regulated Processing of Viral Pre-mRNA
    29. Editing of Viral mRNAs
    30. Export of RNAs from the Nucleus
    31. The Cellular Export Machinery Export of Viral mRNA
    32. Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins
    33. Temporal Control of Viral Gene Expression
    34. Viral Proteins Can Inhibit Cellular mRNA Production
    35. Regulation of Turnover of Viral and Cellular mRNAs in the Cytoplasm
    36. Intrinsic Turnover
    37. Regulation of mRNA Stability by Viral Proteins
    38. mRNA Stabilization Can Facilitate Transformation
    39. Nonsense-Mediated mRNA Decay
    40. Noncoding RNAs
    41. Small Interfering RNAs and Micro-RNAs
    42. Long Noncoding RNAs
    43. Circular RNAs
    44. Perspectives
    45. References
    46. Study Questions
14. 9 Replication of DNA Genomes
    1. Introduction
    2. DNA Synthesis by the Cellular Replication Machinery
    3. Eukaryotic Replicons
    4. Cellular Replication Proteins
    5. Mechanisms of Viral DNA Synthesis
    6. Lessons from Simian Virus 40
    7. Replication of Other Viral DNA Genomes
    8. Properties of Viral Replication Origins
    9. Recognition of Viral Replication Origins
    10. Viral DNA Synthesis Machines
    11. Resolution and Processing of Viral Replication Products
    12. Exponential Accumulation of Viral Genomes
    13. Viral Proteins Can Induce Synthesis of Cellular Replication Proteins
    14. Synthesis of Viral Replication Machines and Accessory Enzymes
    15. Viral DNA Replication Independent of Cellular Proteins
    16. Delayed Synthesis of Structural Proteins Prevents Premature Packaging of DNA Templates
    17. Inhibition of Cellular DNA Synthesis
    18. Synthesis of Viral DNA in Specialized Intracellular Compartments
    19. Limited Replication of Viral DNA Genomes
    20. Integrated Parvoviral DNA Can Be Replicated as Part of the Cellular Genome
    21. Different Viral Origins Regulate Replication of Epstein-Barr Virus
    22. Limited and Amplifying Replication from a Single Origin: the Papillomaviruses
    23. Origins of Genetic Diversity in DNA Viruses
    24. Fidelity of Replication by Viral DNA Polymerases
    25. Modulation of the DNA Damage Response
    26. Recombination of Viral Genomes
    27. Perspectives
    28. References
    29. Study Questions
15. 10 Reverse Transcription and Integration
    1. Retroviral Reverse Transcription
    2. Discovery
    3. Impact
    4. The Process of Reverse Transcription
    5. General Properties and Structure of Retroviral Reverse Transcriptases
    6. Other Examples of Reverse Transcription
    7. Retroviral DNA Integration
    8. The Pathway of Integration: Integrase-Catalyzed Steps
    9. Integrase Structure and Mechanism
    10. Hepadnaviral Reverse Transcription
    11. A DNA Virus with Reverse Transcriptase
    12. The Process of Hepadnaviral Reverse Transcription
    13. Perspectives
    14. References
    15. Study Questions
16. 11 Protein Synthesis
    1. Introduction
    2. Mechanisms of Eukaryotic Protein Synthesis
    3. General Structure of Eukaryotic mRNA
    4. The Translation Machinery
    5. Initiation
    6. Elongation and Termination
    7. The Diversity of Viral Translation Strategies
    8. Polyprotein Synthesis
    9. Leaky Scanning
    10. Reinitiation
    11. StopGo Translation
    12. Suppression of Termination
    13. Ribosomal Frameshifting
    14. Bicistronic mRNAs
    15. Regulation of Translation during Viral Infection
    16. Inhibition of Translation Initiation after Viral Infection
    17. Regulation of eIF4F
    18. Regulation of Poly(A)-Binding Protein Activity
    19. Regulation of eIF3
    20. Interfering with RNA
    21. Stress-Associated RNA Granules
    22. Perspectives
    23. References
    24. Study Questions
17. 12 Intracellular Trafficking
    1. Introduction
    2. Assembly within the Nucleus
    3. Import of Viral Proteins for Assembly
    4. Assembly at the Plasma Membrane
    5. Transport of Viral Membrane Proteins to the Plasma Membrane
    6. Sorting of Viral Proteins in Polarized Cells
    7. Disruption of the Secretory Pathway in Virus-Infected Cells
    8. Signal Sequence-Independent Transport of Viral Proteins to the Plasma Membrane
    9. Interactions with Internal Cellular Membranes
    10. Localization of Viral Proteins to Compartments of the Secretory Pathway
    11. Localization of Viral Proteins to the Nuclear Membrane
    12. Transport of Viral Genomes to Assembly Sites
    13. Transport of Genomic and Pregenomic RNA from the Nucleus to the Cytoplasm
    14. Transport of Genomes from the Cytoplasm to the Plasma Membrane
    15. Perspectives
    16. References
    17. Study Questions
18. 13 Assembly, Release, and Maturation
    1. Introduction
    2. Methods of Studying Virus Assembly and Egress
    3. Structural Studies of Virus Particles
    4. Visualization of Assembly and Exit by Microscopy
    5. Biochemical and Genetic Analyses of Assembly Intermediates
    6. Methods Based on Recombinant DNA Technology
    7. Assembly of Protein Shells
    8. Formation of Structural Units
    9. Capsid and Nucleocapsid Assembly
    10. Self-Assembly and Assisted Assembly Reactions
    11. Selective Packaging of the Viral Genome and Other Components of Virus Particles
    12. Concerted or Sequential Assembly
    13. Recognition and Packaging of the Nucleic Acid Genome
    14. Incorporation of Enzymes and Other Nonstructural Proteins
    15. Acquisition of an Envelope
    16. Sequential Assembly of Internal Components and Budding from a Cellular Membrane
    17. Coordination of the Assembly of Internal Structures with Acquisition of the Envelope
    18. Release of Virus Particles
    19. Assembly and Budding at the Plasma Membrane
    20. Assembly at Internal Membranes: the Problem of Exocytosis
    21. Release of Nonenveloped Virus Particles
    22. Maturation of Progeny Virus Particles
    23. Proteolytic Processing of Structural Proteins
    24. Other Maturation Reactions
    25. Cell-to-Cell Spread
    26. Perspectives
    27. References
    28. Study Questions
19. 14 The Infected Cell
    1. Introduction
    2. Signal Transduction
    3. Signaling Pathways
    4. Signaling in Virus-Infected Cells
    5. Gene Expression
    6. Inhibition of Cellular Gene Expression
    7. Differential Regulation of Cellular Gene Expression
    8. Metabolism
    9. Methods To Study Metabolism
    10. Glucose Metabolism
    11. The Citric Acid Cycle
    12. Electron Transport and Oxidative Phosphorylation
    13. Lipid Metabolism
    14. Remodeling of Cellular Organelles
    15. The Nucleus
    16. The Cytoplasm
    17. Perspectives
    18. References
    19. Study Questions
    20. APPENDIX Structure, Genome Organization, and Infectious Cycles of Viruses Featured in this Book
    21. Glossary
    22. Index
20. Volume 2
21. Preface
22. Acknowledgments
23. About the Authors
24. 1 Infections of Populations: History and Epidemiology
    1. Introduction to Viral Pathogenesis
    2. A Brief History of Viral Pathogenesis
    3. The Relationships among Microbes and the Diseases They Cause
    4. The First Human Viruses Identified and the Role of Serendipity
    5. New Methods Facilitate the Study of Viruses as Causes of Disease
    6. Viral Epidemics in History
    7. Epidemics Shaped History: the 1793 Yellow Fever Epidemic in Philadelphia
    8. Tracking Epidemics by Sequencing: West Nile Virus Spread to the Western Hemisphere
    9. Zoonotic Infections and Epidemics Caused by “New” Viruses
    10. The Economic Toll of Viral Epidemics in Livestock
    11. Population Density and World Travel Are Accelerators of Viral Transmission
    12. Focus on Frontline Health Care: Ebolavirus in Africa
    13. Emergence of a Birth Defect Associated with Infection: Zika Virus in Brazil
    14. Epidemiology
    15. Fundamental Concepts
    16. Methods Used by Epidemiologists
    17. Surveillance
    18. Network Theory and Practical Applications
    19. Parameters That Govern the Ability of a Virus to Infect a Population
    20. Geography and Population Density
    21. Climate
    22. Perspectives
    23. References
    24. Study Questions
25. 2 Barriers to Infection
    1. Introduction
    2. An Overview of Infection and Immunity
    3. A Game of Chess Played by Masters
    4. Initiating an Infection
    5. Successful Infections Must Modulate or Bypass Host Defenses
    6. Skin
    7. Respiratory Tract
    8. Alimentary Tract
    9. Eyes
    10. Urogenital Tract
    11. Placenta
    12. Viral Tropism
    13. Accessibility of Viral Receptors
    14. Other Host-Virus Interactions That Regulate the Infectious Cycle
    15. Spread throughout the Host
    16. Hematogenous Spread
    17. Neural Spread
    18. Organ Invasion
    19. Entry into Organs with Sinusoids
    20. Entry into Organs That Lack Sinusoids
    21. Organs with Dense Basement Membranes
    22. Skin
    23. Shedding of Virus Particles
    24. Respiratory Secretions
    25. Saliva
    26. Feces
    27. Blood
    28. Urine
    29. Semen
    30. Milk
    31. Skin Lesions
    32. Tears
    33. Perspectives
    34. References
    35. Study Questions
26. 3 The Early Host Response: Cell Autonomous and Innate Immunity
    1. Introduction
    2. The First Critical Moments: How Do Individual Cells Detect a Virus Infection?
    3. Cell Signaling Induced by Viral Entry Receptor Engagement
    4. Receptor-Mediated Recognition of Microbe-Associated Molecular Patterns
    5. Cell Intrinsic Defenses
    6. Apoptosis (Programmed Cell Death)
    7. Necroptosis and Other Cell Death Pathways
    8. Autophagy
    9. Epigenetic Silencing
    10. Cellular Restriction Factors
    11. RNA Interference
    12. CRISPR
    13. The Continuum Between Intrinsic and Innate Immunity
    14. Secreted Immune Mediators of the Innate Immune Response
    15. Overview of Cytokine Functions
    16. Interferons, Cytokines of Early Warning and Action
    17. Chemokines
    18. The Innate Immune Response
    19. Monocytes/macrophages
    20. Complement
    21. Natural Killer Cells
    22. Innate Lymphoid Cells
    23. Other Innate Immune Cells of Relevance to Viral Infections
    24. Perspectives
    25. References
    26. Study Questions
27. 4 Adaptive Immunity and the Establishment of Memory
    1. Introduction
    2. Attributes of the Host Response
    3. Speed
    4. Diversity and Specificity
    5. Memory
    6. Self-Control
    7. Lymphocyte Development, Diversity, and Activation
    8. The Hematopoietic Stem Cell Lineage
    9. The Two Arms of Adaptive Immunity
    10. The Major Effectors of the Adaptive Response: B and T Cells
    11. Diverse Receptors Impart Antigen Specificity to B and T Cells
    12. Events at the Site of Infection Set the Stage for the Adaptive Response
    13. Acquisition of Viral Proteins by Professional Antigen-Presenting Cells Enables Production of Proinflammatory Cytokines and Establishment of Inflammation
    14. Activated Antigen-Presenting Cells Leave the Site of Infection and Migrate to Lymph Nodes
    15. Antigen Processing and Presentation
    16. Professional Antigen-Presenting Cells Induce Activation via Costimulation
    17. Presentation of Antigens by Class I and Class II MHC Proteins
    18. Lymphocyte Activation Triggers Massive Cell Proliferation
    19. The CTL (Cell-Mediated) Response
    20. CTLs Lyse Virus-Infected Cells
    21. Control of CTL Proliferation
    22. Control of Infection by T Cells without Killing
    23. Rashes and Poxes
    24. The Humoral (Antibody) Response
    25. Antibodies Are Made by Plasma Cells
    26. Types and Functions of Antibodies
    27. Virus Neutralization by Antibodies
    28. Antibody-Dependent Cell-Mediated Cytotoxicity: Specific Killing by Nonspecific Cells
    29. Immunological Memory
    30. Perspectives
    31. References
    32. Study Questions
28. 5 Patterns and Pathogenesis
    1. Introduction
    2. Animal Models of Human Diseases
    3. Patterns of Infection
    4. Incubation Periods
    5. Mathematics of Growth Correlate with Patterns of Infection
    6. Acute Infections
    7. Persistent Infections
    8. Latent Infections
    9. Abortive Infections
    10. Transforming Infections
    11. Viral Virulence
    12. Measuring Viral Virulence
    13. Alteration of Viral Virulence
    14. Viral Virulence Genes
    15. Pathogenesis
    16. Infected Cell Lysis
    17. Immunopathology
    18. Immunosuppression Induced by Viral Infection
    19. Oncogenesis
    20. Molecular Mimicry
    21. Perspectives
    22. References
    23. Study Questions
29. 6 Cellular Transformation and Oncogenesis
    1. Introduction
    2. Properties of Transformed Cells
    3. Control of Cell Proliferation
    4. Oncogenic Viruses
    5. Discovery of Oncogenic Viruses
    6. Viral Genetic Information in Transformed Cells
    7. The Origin and Nature of Viral Transforming Genes
    8. Functions of Viral Transforming Proteins
    9. Activation of Cellular Signal Transduction Pathways by Viral Transforming Proteins
    10. Viral Signaling Molecules Acquired from the Cell
    11. Alteration of the Production or Activity of Cellular Signal Transduction Proteins
    12. Disruption of Cell Cycle Control Pathways by Viral Transforming Proteins
    13. Abrogation of Restriction Point Control Exerted by the RB Protein
    14. Production of Virus-Specific Cyclins
    15. Inactivation of Cyclin-Dependent Kinase Inhibitors
    16. Transformed Cells Increase in Size and Survive
    17. Mechanisms That Permit Survival of Transformed Cells
    18. Tumorigenesis Requires Additional Changes in the Properties of Transformed Cells
    19. Inhibition of Immune Defenses
    20. Other Mechanisms of Transformation and Oncogenesis by Human Tumor Viruses
    21. Nontransducing Oncogenic Retroviruses: Tumorigenesis with Very Long Latency
    22. Oncogenesis by Hepatitis Viruses
    23. Perspectives
    24. References
    25. Study Questions
30. 7 Vaccines
    1. Introduction
    2. The Origins of Vaccination
    3. Smallpox: a Historical Perspective
    4. Worldwide Vaccination Programs Can Be Dramatically Effective
    5. Vaccine Basics
    6. Immunization Can Be Active or Passive
    7. Active Vaccination Strategies Stimulate Immune Memory
    8. The Fundamental Challenge
    9. The Science and Art of Making Vaccines
    10. Inactivated Virus Vaccines
    11. Attenuated Virus Vaccines
    12. Subunit Vaccines
    13. Virus-Like Particles
    14. Nucleic Acid Vaccines
    15. Vaccine Technology: Delivery and Improving Antigenicity
    16. Adjuvants Stimulate an Immune Response
    17. Delivery and Formulation
    18. Immunotherapy
    19. The Ongoing Quest for an AIDS Vaccine
    20. Perspectives
    21. References
    22. Study Question Puzzle
31. 8 Antiviral Drugs
    1.  Introduction
    2. A Brief History of Antiviral Drug Discovery
    3. Discovering Antiviral Compounds
    4. The Lexicon of Antiviral Discovery
    5. Screening for Antiviral Compounds
    6. Computational Approaches to Drug Discovery
    7. The Difference between “R” and “D”
    8. Drug Resistance
    9. Examples of Antiviral Drugs
    10. Inhibitors of Virus Attachment and Entry
    11. Inhibitors of Viral Nucleic Acid Synthesis
    12. Inhibition of Viral Polyprotein Processing and Assembly
    13. Inhibition of Virus Particle Release
    14. Expanding Targets for Antiviral Drug Development
    15. Attachment and Entry Inhibitors
    16. Nucleic Acid-Based Approaches
    17. Proteases and Nucleic Acid Synthesis and Processing Enzymes
    18. Virus Particle Assembly
    19. Microbicides
    20. Two Stories of Antiviral Success
    21. Combination Therapy
    22. Challenges Remaining
    23. Perspectives
    24. References
    25. Study Questions
32. 9 Therapeutic Viruses
    1. Introduction
    2. Phage Therapy
    3. History
    4. Some Advantages and Limitations of Phage Therapy
    5. Applications in the Clinic and for Disease Prevention
    6. Future Prospects
    7. Oncolytic Animal Viruses
    8. From Anecdotal Reports to Controlled Clinical Trials
    9. Rational Design of Oncolytic Viruses
    10. Two Clinically Approved Oncolytic Viruses
    11. Future Directions
    12. Gene Therapy
    13. Introduction
    14. Retroviral Vectors
    15. Adenovirus-Associated Virus Vectors
    16. Future Prospects
    17. Vaccine Vectors
    18. DNA Viruses
    19. RNA Viruses
    20. Perspectives
    21. References
    22. Study Questions
33. 10 Virus Evolution
    1. Virus Evolution
    2. How Do Virus Populations Evolve?
    3. Two General Virus Survival Strategies Can Be Distinguished
    4. Large Numbers of Viral Progeny and Mutants Are Produced in Infected Cells
    5. The Quasispecies Concept
    6. Genetic Shift and Genetic Drift
    7. Fundamental Properties of Viruses That Constrain Evolution
    8. Two General Pathways for Virus Evolution
    9. Evolution of Virulence
    10. The Origin of Viruses
    11. When and How Did They Arise?
    12. Evolution of Contemporary Eukaryotic Viruses
    13. Host-Virus Relationships Drive Evolution
    14. DNA Virus-Host Relationships
    15. RNA Virus-Host Relationships
    16. The Host-Virus “Arms Race”
    17. Lessons from Paleovirology
    18. Endogenous Retroviruses
    19. DNA Fossils Derived from Other RNA Viral Genomes
    20. Endogenous Sequences from DNA Viruses
    21. Short- versus Long-Term Rates of Viral Evolution
    22. Perspectives
    23. References
    24. Study Questions
34. 11 Emergence
    1.  The Spectrum of Host-Virus Interactions
    2. Stable Interactions
    3. The Evolving Host-Virus Interaction
    4. The Dead-End Interaction
    5. The Resistant Host
    6. Encountering New Hosts: Humans Constantly Provide New Venues for Infection
    7. Common Sources for Animal-to-Human Transmission
    8. Viral Diseases That Illustrate the Drivers of Emergence
    9. Poliomyelitis: Unexpected Consequences of Modern Sanitation
    10. Introduction of Viruses into Naïve Populations
    11. Hantavirus Pulmonary Syndrome: Changing Animal Populations
    12. Severe Acute and Middle East Respiratory Syndromes (SARS and MERS): Zoonotic Coronavirus Infections
    13. The Contribution to Emergence of Mutation, Recombination, or Reassortment
    14. Canine Parvoviruses: Cat-to-Dog Host Range Switch by Two Amino Acid Changes
    15. Influenza Epidemics and Pandemics: Escaping the Immune Response by Reassortment
    16. New Technologies Uncover Previously Unrecognized Viruses
    17. Hepatitis Viruses in the Human Blood Supply
    18. A Revolution in Virus Discovery
    19. Perceptions and Possibilities
    20. Virus Names Can Be Misleading
    21. All Viruses Are Important
    22. Can We Predict the Next Viral Pandemic?
    23. Preventing Emerging Virus Infections
    24. Perspectives
    25. References
    26. Study Questions
35. 12 Human Immunodeficiency Virus Type I Pathogenesis
    1. Introduction
    2. Worldwide Impact of AIDS
    3. HIV-1 Is a Lentivirus
    4. Discovery and Characterization
    5. Distinctive Features of the HIV-1 Reproduction Cycle and the Functions of HIV-1 Proteins
    6. The Viral Capsid Counters Intrinsic Defense Mechanisms
    7. Entry and Transmission
    8. Entry in the Cell
    9. Entry into the Body
    10. Transmissions in Human Populations
    11. The Course of Infection
    12. The Acute Phase
    13. The Asymptomatic Phase
    14. The Symptomatic Phase and AIDS
    15. Effects of HIV-1 on Other Tissues and Organs
    16. Virus Reproduction
    17. Dynamics in the Absence of Treatment
    18. Dynamics of Virus Reproduction during Treatment
    19. Latency
    20. Immune Responses to HIV-1
    21. Innate Response
    22. Humoral Responses
    23. HIV-1 and Cancer
    24. Kaposi’s Sarcoma
    25. B-Cell Lymphomas
    26. Anogenital Carcinomas
    27. Prospects for Treatment and Prevention
    28. Antiviral Drugs
    29. Confronting the Problems of Persistence and Latency
    30. Gene Therapy Approaches
    31. Immune System-Based Therapies
    32. Antiviral Drug Prophylaxis
    33. Perspectives
    34. References
36. 13 Unusual Infectious Agents
    1. Introduction
    2. Viroids
    3. Replication
    4. Sequence Diversity
    5. Movement
    6. Pathogenesis
    7. Satellite Viruses and RNAs
    8. Replication
    9. Pathogenesis
    10. Hepatitis Delta Virus
    11. Prions and Transmissible Spongiform Encephalopathies
    12. Scrapie
    13. Physical Properties of the Scrapie Agent
    14. Human TSEs
    15. Hallmarks of TSE Pathogenesis
    16. Prions and the prnp Gene
    17. Prion Strains
    18. Bovine Spongiform Encephalopathy
    19. Chronic Wasting Disease
    20. Treatment of Prion Diseases
    21. Perspectives
    22. References
    23. Study Questions
    24. APPENDIX Epidemiology and Pathogenesis of Selected Human Viruses
    25. Glossary
    26. Index

Author Biography

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.