Оглавление
S. Jane Flint. Principles of Virology, Volume 2
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
VOLUME II Pathogenesis and Control. PRINCIPLES OF. Virology
About the Instructor Companion Website
Preface
What’s New
Principles Taught in Two Distinct, but Integrated Volumes
Volume I: The Science of Virology and the Molecular Biology of Viruses
Volume II: Pathogenesis, Control, and Evolution
Acknowledgments
About the Authors
Key of Repetitive Elements
1 Infections of Populations: History and Epidemiology
LINKS FOR CHAPTER 1
Introduction to Viral Pathogenesis
PRINCIPLES Introduction to viral pathogenesis
A Brief History of Viral Pathogenesis. The Relationships among Microbes and the Diseases They Cause
BOX 1.1. DISCUSSION. Why viruses may not fulfill Koch’s postulates
The First Human Viruses Identified and the Role of Serendipity
BOX 1.2. BACKGROUND. Mosquito control measures
New Methods Facilitate the Study of Viruses as Causes of Disease
Viral Epidemics in History
BOX 1.3. METHODS. Nanopore sequencing
Epidemics Shaped History: the 1793 Yellow Fever Epidemic in Philadelphia
Tracking Epidemics by Sequencing: West Nile Virus Spread to the Western Hemisphere
Zoonotic Infections and Epidemics Caused by “New” Viruses
The Economic Toll of Viral Epidemics in Livestock
Population Density and World Travel Are Accelerators of Viral Transmission
Focus on Frontline Health Care: Ebolavirus in Africa
Emergence of a Birth Defect Associated with Infection: Zika Virus in Brazil
Epidemiology
Fundamental Concepts. Incidence versus Prevalence
BOX 1.4. DISCUSSION. Video games model infectious-disease epidemics
Prospective and Retrospective Studies
BOX 1.5. TERMINOLOGY. Morbidity, mortality, incidence, and case fatality
Mortality, Morbidity, and Case Fatality Ratios
R-naught (R0)
Methods Used by Epidemiologists
Surveillance
BOX 1.6. METHODS. The use of statistics in virology
BOX 1.7. BACKGROUND. Descriptive epidemiology and the discovery of human immunodeficiency virus
BOX 1.8. METHODS
Network Theory and Practical Applications
Parameters That Govern the Ability of a Virus to Infect a Population
Geography and Population Density
BOX 1.9. DISCUSSION. A virus on the move
Climate
BOX 1.10. EXPERIMENTS. Temperature influences the transmission of influenza virus
BOX 1.11. BACKGROUND
BOX 1.12. DISCUSSION. Plant virus epidemiology
Perspectives
BOX 1.13. DISCUSSION. This moment in time: the SARS-CoV-2 pandemic
REFERENCES. Books
Review Articles
Papers of Special Interest
STUDY QUESTIONS
2 Barriers to Infection
LINKS FOR CHAPTER 2
Introduction
An Overview of Infection and Immunity. A Game of Chess Played by Masters
PRINCIPLES Barriers to infection
BOX 2.1. TERMINOLOGY. Is it evasion or modulation?
Initiating an Infection
Successful Infections Must Modulate or Bypass Host Defenses
Skin
Respiratory Tract
BOX 2.2. EXPERIMENTS. Dermal damage increases immunity and host survival
BOX 2.3. DISCUSSION. In praise of mucus
Alimentary Tract
BOX 2.4. EXPERIMENTS. Olfactory neurons: front-line sentinels
BOX 2.5. EXPERIMENTS. Commensal bacteria aid virus infections in the gastrointestinal tract
Eyes
Urogenital Tract
Placenta
Viral Tropism
BOX 2.6. DISCUSSION. Is intuition a host defense?
Accessibility of Viral Receptors
Other Host-Virus Interactions That Regulate the Infectious Cycle
BOX 2.7. DISCUSSION. A mechanism for expanding the tropism of influenza virus is revealed by analyzing infections that occurred in 1940
Spread throughout the Host
BOX 2.8. DISCUSSION. Gender differences in infection and disease
Hematogenous Spread
BOX 2.9. TERMINOLOGY. The viruses in your blood
Neural Spread
BOX 2.10. TERMINOLOGY. Infection of the nervous system: definitions and distinctions
Organ Invasion
Entry into Organs with Sinusoids
Entry into Organs That Lack Sinusoids
BOX 2.11. TERMINOLOGY. Which direction: anterograde or retrograde?
Organs with Dense Basement Membranes
Skin
Shedding of Virus Particles
Respiratory Secretions
Saliva
Feces
BOX 2.12. DISCUSSION. A ferret model of influenza virus infection ignites irrational fears
Blood
Urine
Semen
Milk
Skin Lesions
Tears
Perspectives
BOX 2.13. DISCUSSION. Chicken pox parties
REFERENCES. Books
Review Articles
Papers of Special Interest
STUDY QUESTIONS
3 The Early Host Response: Cell-Autonomous and Innate Immunity
LINKS FOR CHAPTER 3
Introduction
PRINCIPLES The early host response: cell-autonomous and innate immunity
BOX 3.1. WARNING. Everything is intertwined
The First Critical Moments: How Do Individual Cells Detect a Virus Infection?
BOX 3.2. TERMINOLOGY. Intrinsic or innate?
Cell Signaling Induced by Viral Entry Receptor Engagement
Receptor-Mediated Recognition of Microbe-Associated Molecular Patterns
Toll-Like Receptors (TLRs)
BOX 3.3. TRAILBLAZER. Toll receptors: the fruit fly connection
BOX 3.4. BACKGROUND. Plants produce proteins that are both “detectors” and “alarms”
RIG-I-Like Receptors (RLRs)
Cytoplasmic DNA Sensors
Viral proteins antagonize pattern recognition receptors
BOX 3.5. EXPERIMENTS. A viral DNA sensor moonlights as a sensor for the RNA virus influenza A virus
Cell-Intrinsic Defenses
Apoptosis (Programmed Cell Death)
BOX 3.6. DISCUSSION. A new function for oncoproteins of DNA tumor viruses
BOX 3.7. TERMINOLOGY. What to do with the second “p”?
Apoptosis Is a Defense against Viral Infection
Viral Gene Products That Modulate Apoptosis
Apoptosis Is Monitored by Sentinel Cells
Programmed Necrosis (Necroptosis)
Autophagy
Epigenetic Silencing
Host Proteins That Restrict Virus Reproduction (Restriction Factors)
Targeting Viral Genomes
BOX 3.8. EXPERIMENTS. Epigenetic silencing of unintegrated retroviral DNA
Deaminases
Targeting Genome Synthesis
Targeting Trafficking of Viral Components
Targeting Release of Virus Particles
Targeting Everything: TRIM, a Family of Divergent Antiviral Proteins
RNA Interference
CRISPRs
The Continuum between Intrinsic and Innate Immunity
Secreted Mediators of the Innate Immune Response
BOX 3.9. BACKGROUND. Ancient mechanisms of immunity
Overview of Cytokine Functions
BOX 3.10. EXPERIMENTS. O-linked sugars as very early warning signals
Interferons, Cytokines of Early Warning and Action
BOX 3.11. TERMINOLOGY. Infiltration and inflammation
BOX 3.12. TRAILBLAZER. The interferon system is crucial for antiviral defense
Type I IFN Synthesis
BOX 3.13. DISCUSSION. A gut feeling about a new interferon type
BOX 3.14. DISCUSSION. Switching IFN-β transcription on and off
IFN Signaling
IFN Produces an Antiviral State
Some IFN-Induced Gene Products and Their Antiviral Actions
RNase L and 2′ -5′ -oligo(A) Synthetases
Regulators of the IFN Response
Viral Gene Products That Counter the IFN Response
Chemokines
The Innate Immune Response
Monocytes, Macrophages, and Dendritic Cells
Complement
The Complement Cascade
BOX 3.15. DISCUSSION. The complement system has four major biological functions
“Natural Antibody” Protects against Infection
Regulation of the Complement Cascade
Natural Killer Cells
NK-Cell Recognition of Infected Cells: Detection of “Missing Self” or “Altered Self” Signals
MHC Class I Receptors on NK Cells Produce Inhibitory Signals
Viral Proteins Modulate NK-Cell Actions
NK-Cell Memory
Other Innate Immune Cells Relevant to Viral Infections
Neutrophils
γδ Cells
Innate Lymphoid Cells
Perspectives
REFERENCES. Books
Reviews
Classic Papers
Selected Papers
STUDY QUESTIONS
4 Adaptive Immunity and the Establishment of Memory
LINKS FOR CHAPTER 4
Introduction
Attributes of the Host Response. Speed
PRINCIPLES Adaptive immunity and the establishment of memory
Diversity and Specificity
Memory
BOX 4.1. TERMINOLOGY. Pathogens, antigens, and epitopes
Self-Control
Lymphocyte Development, Diversity, and Activation
The Hematopoietic Stem Cell Lineage
BOX 4.2. TERMINOLOGY. Leukocytes and lymphocytes
The Two Arms of Adaptive Immunity
The Major Effectors of the Adaptive Response: B and T Cells
B Cells
T Cells
BOX 4.3. METHODS. Flow cytometry
Box 4.4. DISCUSSION. The well-protected thymus
Diverse Receptors Impart Antigen Specificity to B and T Cells
BOX 4.5. DISCUSSION. Convergent evolution of host proteins that bind to viral epitopes
Events at the Site of Infection Set the Stage for the Adaptive Response
Acquisition of Viral Proteins by Professional Antigen-Presenting Cells Enables Production of Proinflammatory Cytokines and Establishment of Inflammation
The Inflammasome and Cytokine Release
Inflammation
Activated Antigen-Presenting Cells Leave the Site of Infection and Migrate to Lymph Nodes
BOX 4.6. BACKGROUND. Infection of the sentinels: dysfunctional immune modulation
Antigen Processing and Presentation. Professional Antigen-Presenting Cells Induce Activation via Costimulation
Presentation of Antigens by Class I and Class II MHC Proteins
Cytotoxic T Cells Recognize Infected Cells by Engaging MHC Class I Receptors
BOX 4.7. TRAILBLAZER. Virology provides Nobel Prize-winning insight: MHC restriction
Th Cells Recognize Professional Antigen-Presenting Cells by Engaging MHC Class II Receptors
Lymphocyte Activation Triggers Massive Cell Proliferation
BOX 4.8. DISCUSSION. Influence of MHC alleles on human partnership and sexual satisfaction
The CTL (Cell-Mediated) Response
CTLs Lyse Virus-Infected Cells
Control of CTL Proliferation
BOX 4.9. BACKGROUND. Interferon γ signaling
BOX 4.10. METHODS. Measuring the antiviral cellular immune response
Control of Infection by CTLs without Killing
Rashes and Poxes
BOX 4.11. DISCUSSION. The immune system within the brain
The Humoral (Antibody) Response. Antibodies Are Made by Plasma Cells
Types and Functions of Antibodies
Virus Neutralization by Antibodies
Antibody-Dependent Cell-Mediated Cytotoxicity: Specific Killing by Nonspecific Cells
Immunological Memory
Perspectives
REFERENCES. Books
Reviews
Classic Papers
Selected Papers
STUDY QUESTION PUZZLE
5 Patterns and Pathogenesis
LINKS FOR CHAPTER 5
Introduction
Animal Models of Human Diseases
PRINCIPLES Patterns and pathogenesis
BOX 5.1. BACKGROUND. A 2,500-year-old smallpox case study
BOX 5.2. WARNING. Of mice and cells
BOX 5.3. METHODS. Genetically engineered mouse models for studying viral pathogenesis
BOX 5.4. WARNING. The dangers of inbreeding
Patterns of Infection
Incubation Periods
Mathematics of Growth Correlate with Patterns of Infection
Acute Infections
BOX 5.5. METHODS. Mathematical approaches to understanding viral population dynamics
BOX 5.6. DISCUSSION. Norovirus: the “two-bucket virus”
BOX 5.7. DISCUSSION. Poliovirus escape antibodies
Acute Infections Pose Common Public Health Problems
Persistent Infections
Multiple Cellular Mechanisms Promote Viral Persistence
Modulation of the Adaptive Immune Response Can Perpetuate a Persistent Infection
Persistent Infections May Be Established in Tissues with Reduced Immune Surveillance
Persistent Infections May Be Established in Cells of the Immune System
Examples of Viruses That Cause Persistent Infections
BOX 5.8. TERMINOLOGY
Latent Infections
Herpes Simplex Virus
BOX 5.9. DISCUSSION. The hygiene hypothesis: why people vary in their response to herpes simplex virus infection
BOX 5.10. DISCUSSION
Epstein-Barr Virus
BOX 5.11. DISCUSSION. Epstein-Barr virus, depression, and pregnancy
Abortive Infections
Transforming Infections
Viral Virulence
Measuring Viral Virulence
BOX 5.12. TERMINOLOGY. Measures of viral virulence
Approaches To Identify Viral Genes That Contribute to Virulence
BOX 5.13. EXPERIMENTS. Viral virulence is dependent on multiple parameters
Viral Virulence Genes
BOX 5.14. TERMINOLOGY. Four classes of viral virulence genes
Gene Products That Alter Virus Reproduction
BOX 5.15. EXPERIMENTS. Inadvertent creation of a more virulent poxvirus
Noncoding Sequences That Affect Virus Reproduction
Gene Products That Modify Host Defense Mechanisms
Gene Products That Enable the Virus To Spread in the Host
BOX 5.16. DISCUSSION
Pathogenesis
Infected Cell Lysis
Immunopathology
Immunopathological Lesions
Superantigens “Short-Circuit” the Immune System
Damage Mediated by Free Radicals
Immunosuppression Induced by Viral Infection
Oncogenesis
Molecular Mimicry
Perspectives
BOX 5.17. EXPERIMENTS. Viral infections promote or protect against autoimmune disease
REFERENCES. Books
Reviews
Papers of Special Interest
STUDY QUESTIONS
6 Cellular Transformation and Oncogenesis
LINKS FOR CHAPTER 6
Introduction
Properties of Transformed Cells. Cellular Transformation
PRINCIPLES Cellular transformation and oncogenesis
BOX 6.1. TERMINOLOGY. Some cancer terms
BOX 6.2. BACKGROUND. Genetic alterations associated with the development of cancer
BOX 6.3. BACKGROUND. Telomeres, telomerase, and cellular immortality
Properties That Distinguish Transformed from Normal Cells
Control of Cell Proliferation. Sensing the Environment
Integration of Mitogenic and Growth-Promoting Signals
Regulation of the Cell Cycle
The Cell Cycle Engine
Oncogenic Viruses
Discovery of Oncogenic Viruses. Retroviruses
BOX 6.4. EXPERIMENTS. A cancer virus with genomic features of both papillomaviruses and polyomaviruses
Oncogenic DNA Viruses
BOX 6.5. DISCUSSION. Walleye dermal sarcoma virus, a retrovirus with a unique transmission cycle
Recent Identification of Oncogenic Viruses
Common Properties of Oncogenic Viruses
Viral Genetic Information in Transformed Cells. State of Viral DNA
BOX 6.6. DISCUSSION. A polyomavirus that contributes to development of Merkel cell carcinoma in humans
Identification and Properties of Viral Transforming Genes
BOX 6.7. TRAILBLAZER. Identification of the transforming proteins of simian virus 40
BOX 6.8. TRAILBLAZER. Preparation of the first oncogene probe
The Origin and Nature of Viral Transforming Genes
Functions of Viral Transforming Proteins
Activation of Cellular Signal Transduction Pathways by Viral Transforming Proteins
Viral Signaling Molecules Acquired from the Cell. The Transduced Cellular Genes of Acutely Transforming Retroviruses
Viral Homologs of Cellular Genes
Alteration of the Production or Activity of Cellular Signal Transduction Proteins. Insertional Activation by Nontransducing Retroviruses
Viral Proteins That Alter Cellular Signaling Pathways
BOX 6.9. DISCUSSION. Transformation by remote control?
Alteration of the Activities of Cellular Signal Transduction Molecules
Disruption of Cell Cycle Control Pathways by Viral Transforming Proteins
Abrogation of Restriction Point Control Exerted by the RB Protein. The Restriction Point in Mammalian Cells
Viral Proteins Prevent Negative Regulation by RB and Related Proteins
Production of Virus-Specific Cyclins
Inactivation of Cyclin-Dependent Kinase Inhibitors
Transformed Cells Increase in Size and Survive
Mechanisms That Permit Survival of Transformed Cells
Viral Inhibitors of the Apoptotic Cascade
Integration of Inhibition of Apoptosis with Stimulation of Proliferation
Inactivation of the Cellular Tumor Suppressor p53
Tumorigenesis Requires Additional Changes in the Properties of Transformed Cells
Inhibition of Immune Defenses
Other Mechanisms of Transformation and Oncogenesis by Human Tumor Viruses
Nontransducing Oncogenic Retroviruses: Tumorigenesis with Very Long Latency
Oncogenesis by Hepatitis Viruses. Hepatitis B Virus
Hepatitis C Virus
Perspectives
REFERENCES. Chapters in Books
Review Articles
Papers of Special Interest
STUDY QUESTIONS
7 Vaccines
LINKS FOR CHAPTER 7
Introduction
The Origins of Vaccination. Smallpox: a Historical Perspective
PRINCIPLES Vaccines
Worldwide Vaccination Programs Can Be Dramatically Effective
Box 7.1. BACKGROUND. Whither the milkmaid?
Eradicating a Viral Disease: Is It Possible?
BOX 7.2. BACKGROUND. The current U.S. smallpox vaccine
BOX 7.3. DISCUSSION. Should laboratory stocks of smallpox virus be destroyed?
BOX 7.4. TRAILBLAZER. Rinderpest virus: the other eradicated virus
National Programs for Eradication of Agriculturally Important Viral Diseases Differ Substantially from Global Programs
BOX 7.5. DISCUSSION. The poliomyelitis eradication effort: should vaccine eradication be next?
Vaccine Basics. Immunization Can Be Active or Passive
Active Vaccination Strategies Stimulate Immune Memory
BOX 7.6. EXPERIMENTS. A historical example that underscores the principle of long-lasting immune memory
Protection from Infection or Protection from Disease?
Vaccines Must Be Safe, Efficacious, and Practical
BOX 7.7. DISCUSSION. The public’s view of risk-taking is a changing landscape
BOX 7.8. DISCUSSION. National vaccine programs depend on public acceptance of their value
BOX 7.9. METHODS. Development of new delivery vehicles for vaccines
The Fundamental Challenge
The Science and Art of Making Vaccines
BOX 7.10. DISCUSSION. Delivering vaccines to people in hard-to-reach locations
BOX 7.11. TERMINOLOGY. Live and let die
Inactivated Virus Vaccines
BOX 7.12. WARNING. Amplification of influenza virus in eggs leads to mutations that limit antigenicity
Attenuated Virus Vaccines
BOX 7.13. BACKGROUND. Shingles vaccines
BOX 7.14. DISCUSSION. Vaccine adverse event reporting
Subunit Vaccines
BOX 7.15. DISCUSSION. Plant-based vaccines
BOX 7.16. DISCUSSION. Accidental infections “in the wild”
Virus-Like Particles
BOX 7.17. TRAILBLAZER. Development of the first anticancer vaccine
Nucleic Acid Vaccines
BOX 7.18. DISCUSSION. Should men be encouraged to get the human papillomavirus vaccine?
Vaccine Technology: Delivery and Improving Antigenicity. Adjuvants Stimulate an Immune Response
Delivery and Formulation
Immunotherapy
The Ongoing Quest for an AIDS Vaccine
Perspectives
REFERENCES. Books
Historical Papers and Books
Reviews
Selected Papers
STUDY QUESTION PUZZLE
8 Antiviral Drugs
LINKS FOR CHAPTER 8
Introduction
A Brief History of Antiviral Drug Discovery
PRINCIPLES Antiviral drugs
Discovering Antiviral Compounds
The Lexicon of Antiviral Discovery
Screening for Antiviral Compounds. Viral targets
Host targets
Mechanism-Based Screens
Cell-Based Screens
High-Throughput Screens
Sources of Chemical Compounds Used in Screening
Computational Approaches to Drug Discovery. Structure-Assisted Drug Design
Genome Sequencing and Other Advances Expose New Targets for Antiviral Drugs
In Silico Drug Discovery via Virtual Screening
BOX 8.1. EXPERIMENTS. An allosteric antiviral by in silico design
The Difference between “R” and “D” Antiviral Drugs Are Expensive To Discover, Develop, and Bring to the Market
BOX 8.2. DISCUSSION. New drugs, new mechanisms—no interest?
BOX 8.3. TERMINOLOGY. Clinical trials
Antiviral Drugs Must Be Safe
Drug Formulation and Delivery
Drug Resistance
Examples of Antiviral Drugs
Inhibitors of Virus Attachment and Entry
BOX 8.4. TERMINOLOGY. What’s in a name?
Maraviroc (Selzentry), Human Immunodeficiency Virus Type 1 Attachment Inhibitor
Enfuvirtide (Fuzeon), Human Immunodeficiency Virus Type 1 Fusion Inhibitor
Amantadine (Symmetrel), Inhibitor of Influenza A Virus Uncoating
Inhibitors of Viral Nucleic Acid Synthesis
Herpesvirus DNA Polymerase Inhibitors
Cidofovir (Vistide), a Broad-Spectrum Antiviral
Azidothymidine (Retrovir), Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitor
Lamivudine (Epivir), Hepatitis B Virus Reverse Transcriptase Inhibitor
Ribavirin (Virazole), an Inhibitor of RNA Viruses
Inhibitors of Hepatitis C Virus RNA Polymerase
Nonnucleoside Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase
Foscarnet (Foscavir), Nonnucleoside Inhibitor of Herpesvirus DNA Synthesis
Baloxavir Marboxil (Xofluza), Inhibitor of Influenza Virus mRNA Synthesis
Inhibitors of Hepatitis C Virus NS5A Protein
Inhibitors of Human Immunodeficiency Virus Type 1 Integrase
Inhibition of Viral Polyprotein Processing and Assembly
Human Immunodeficiency Virus Type 1 Protease Inhibitors
Inhibitors of Hepatitis C Virus Protease
Inhibition of Virus Particle Release. Influenza Virus Neuraminidase Inhibitors
Expanding Targets for Antiviral Drug Development
BOX 8.5. EXPERIMENTS. Inhibitors of influenza virus neuraminidase: development and impact
Attachment and Entry Inhibitors
Nucleic Acid-Based Approaches
Proteases and Nucleic Acid Synthesis and Processing Enzymes
Virus Particle Assembly
Microbicides
Two Stories of Antiviral Success
Combination Therapy
BOX 8.6. EXPERIMENTS. Highly specific, designed inhibitors may have unpredicted activities
Challenges Remaining
Perspectives
BOX 8.7. DISCUSSION. What price drugs?
REFERENCES. Books
Reviews
Papers of Special Interest
Websites
STUDY QUESTIONS
9 Therapeutic Viruses
LINKS FOR CHAPTER 9
Introduction
Phage Therapy. History
PRINCIPLES Therapeutic viruses
Some Advantages and Limitations of Phage Therapy
Applications in the Clinic and for Disease Prevention
BOX 9.1. DISCUSSION. Phage therapy rescues dying patient
Future Prospects
Oncolytic Animal Viruses. From Anecdotal Reports to Controlled Clinical Trials
BOX 9.2. WARNING. Before standardization of clinical trials: some early studies of human viruses to treat cancer in humans
BOX 9.3. DISCUSSION. Multiple mechanisms might contribute to the tumor cell-selective reproduction of ONYX-015 and similar viruses
Rational Design of Oncolytic Viruses
Tumor Cell-Selective Reproduction
Strategies for Increasing Cell Lysis
Promoting Antitumor Immune Responses
BOX 9.4. DISCUSSION. An Achilles’ heel of cancer cells
Two Clinically Approved Oncolytic Viruses. Oncorine
BOX 9.5. BACKGROUND. Corporate struggles and the failure to develop ONYX-015 in the United States
Talimogene Laherparepvec
Future Directions
Gene Therapy. Introduction
Retroviral Vectors. Beneficial Features for Gene Therapy
BOX 9.6. WARNING. Fatality in a gene therapy trial
Overcoming the Limitations of First-Generation Vectors
BOX 9.7. WARNING. Inadvertent insertional activation of a cellular gene during gene transfer
Examples of Clinical Success
CAR T Cells for Cancer Immunotherapy
Other Applications of Retroviral Vectors
Adenovirus-Associated Virus Vectors
Developing and Improving AAV Vectors
Clinical Trials
BOX 9.8. EXPERIMENTS. Reconstruction of an ancestral adenovirus-associated virus
Other Applications of AAV Vectors
Future Prospects
Vaccine Vectors
DNA Viruses. Adenovirus Vectors
Poxvirus Vectors
Adenovirus-Associated Virus Vectors
RNA Viruses. Vesicular Stomatitis Virus Vectors
Flaviviruses and Alphaviruses
Newcastle Disease Virus Vectors
Perspectives
REFERENCES. Review Articles
Papers of Special Interest
Blog Posts
STUDY QUESTIONS
10 Virus Evolution
LINKS FOR CHAPTER 10
Virus Evolution
How Do Virus Populations Evolve?
Two General Virus Survival Strategies Can Be Distinguished
PRINCIPLES Evolution
Large Numbers of Viral Progeny and Mutants Are Produced in Infected Cells
RNA Virus Evolution
DNA Virus Evolution
The Quasispecies Concept
Sequence Conservation in Changing Genomes
The Error Threshold
Genetic Bottlenecks
Genetic Shift and Genetic Drift
Exchange of Genetic Information
BOX 10.1. EXPERIMENT. Does Muller’s ratchet ever occur in nature?
Fundamental Properties of Viruses That Constrain Evolution
Two General Pathways for Virus Evolution
BOX 10.2. BACKGROUND. Reassortment of influenza virus genome segments
Evolution of Virulence
BOX 10.3. BACKGROUND. Evolution by nonhomologous recombination and horizontal gene transfer
BOX 10.4. DISCUSSION. An unexpected constraint on evolution: selection for transmission and survival within a host
The Origin of Viruses. When and How Did They Arise?
Evolution of Contemporary Eukaryotic Viruses
RNA Viruses
The Protovirus Hypothesis for Retroviruses and Relatives
DNA Virus Origins
BOX 10.5. BACKGROUND. Discovery of virus giants: the largest known viral particles and genomes
Host-Virus Relationships Drive Evolution
DNA Virus–Host Relationships. Papillomaviruses and Polyomaviruses
Herpesviruses
RNA Virus-Host Relationships
(–) Strand RNA Viruses
(+) Strand RNA Viruses
The Host–Virus “Arms Race”
BOX 10.6. EXPERIMENTS. A classic experiment in virus evolution: deliberate release of rabbitpox virus in Australia
BOX 10.7. EXPERIMENTS. Host-virus arms race and the transferrin receptor
Lessons from Paleovirology
Endogenous Retroviruses
BOX 10.8. EXPERIMENTS. Retrovirus lineage traced to the Paleozoic Era
DNA Fossils Derived from Other RNA Viral Genomes
Endogenous Sequences from DNA Viruses
BOX 10.9. BACKGROUND. Retroviral Env proteins and evolution of the placenta
Short- versus Long-Term Rates of Viral Evolution
Perspectives
BOX 10.10. BACKGROUND. The world’s supply of human immunodeficiency virus genomes provides remarkable opportunity for selection
REFERENCES
Review Articles
Papers of Special Interest
STUDY QUESTIONS
11 Emergence
LINKS FOR CHAPTER 11
The Spectrum of Host-Virus Interactions
Stable Interactions
PRINCIPLES Emergence
The Evolving Host-Virus Interaction
The Dead-End Interaction
The Resistant Host
BOX 11.1. DISCUSSION. An evolving virus infection: the West Nile virus outbreak
Encountering New Hosts: Humans Constantly Provide New Venues for Infection
Common Sources for Animal-to-Human Transmission
BOX 11.2. DISCUSSION. Why do bats harbor so many viruses?
Viral Diseases That Illustrate the Drivers of Emergence. Poliomyelitis: Unexpected Consequences of Modern Sanitation
Introduction of Viruses into Naïve Populations
BOX 11.3. DISCUSSION. Enterovirus D68, a reemerging pathogen associated with childhood paralysis
Hantavirus Pulmonary Syndrome: Changing Animal Populations
Severe Acute and Middle East Respiratory Syndromes (SARS and MERS): Zoonotic Coronavirus Infections
BOX 11.4. DISCUSSION. Zika virus: new patterns of disease?
The Contribution to Emergence of Mutation, Recombination, or Reassortment
Canine Parvoviruses: Cat-to-Dog Host Range Switch by Two Amino Acid Changes
Influenza Epidemics and Pandemics: Escaping the Immune Response by Reassortment
New Technologies Uncover Previously Unrecognized Viruses
Hepatitis Viruses in the Human Blood Supply
BOX 11.5. DISCUSSION. Avian influenza viruses: scientific and societal implications of transmissibility experiments using animal models
A Revolution in Virus Discovery
BOX 11.6. BACKGROUND. Discovery of hepatitis C virus, a triumph of persistence
Perceptions and Possibilities
Virus Names Can Be Misleading
All Viruses Are Important
Can We Predict the Next Viral Pandemic?
BOX 11.7. DISCUSSION. Viral infections as agents of war and terror
Preventing Emerging Virus Infections
Perspectives
REFERENCES. Books
Review Articles
Papers of Special Interest
STUDY QUESTIONS
12 Human Immunodeficiency Virus Type 1 Pathogenesis
LINKS FOR CHAPTER 12
Introduction. Worldwide Impact of AIDS
HIV-1 Is a Lentivirus. Discovery and Characterization
PRINCIPLES HIV-1 pathogenesis
BOX 12.1. DISCUSSION. Lessons from the discovery of the AIDS virus
Distinctive Features of the HIV-1 Reproductive Cycle and the Functions of HIV-1 Proteins
BOX 12.2. TRAILBLAZER. The earliest records of HIV-1 infection
The Regulatory Proteins Tat and Rev
The Accessory Proteins
BOX 12.3. BACKGROUND. Evolution of tetherin antagonism
The Viral Capsid Counters Intrinsic Defense Mechanisms
BOX 12.4. BACKGROUND. Virus tropism and animal models for HIV-1
Entry and Transmission. Entry into the Cell
Entry into the Body
Transmission in Human Populations
The Course of Infection
The Acute Phase
The Asymptomatic Phase
The Symptomatic Phase and AIDS
Effects of HIV-1 on Other Tissues and Organs
Effects of HIV-1 Infection on the Nervous System
Virus Reproduction. Dynamics in the Absence of Treatment
Dynamics of Virus Reproduction during Treatment
Latency
Immune Responses to HIV-1. Innate Response
Humoral Responses
HIV-1 and Cancer
Kaposi′s Sarcoma
B-Cell Lymphomas
Anogenital Carcinomas
Prospects for Treatment and Prevention. Antiviral Drugs
BOX 12.5. BACKGROUND. The Berlin patient
Confronting the Problems of Persistence and Latency
Gene Therapy Approaches
BOX 12.6. DISCUSSION. CCR5 is the target in the first CRISPR-Cas-edited human embryos
Immune System-Based Therapies
Antiviral Drug Prophylaxis. Preexposure Prophylaxis (PrEP)
Postexposure Prophylaxis (PEP)
Perspectives
REFERENCES. Books
Reviews
Research Articles of Historical Interest
Highlights
Websites
STUDY QUESTIONS
13 Unusual Infectious Agents
LINKS FOR CHAPTER 13
Introduction
Viroids
Replication
PRINCIPLES Unusual infectious agents
BOX 13.1. DISCUSSION. Why do viroids infect only plants?
BOX 13.2. DISCUSSION. Viroids and mutation rates
Sequence Diversity
Movement
Pathogenesis
Satellite Viruses and RNAs
Replication
Pathogenesis
Hepatitis Delta Virus
Prions and Transmissible Spongiform Encephalopathies
Scrapie
BOX 13.3. EXPERIMENTS. Hepatitis delta-like viruses in birds and snakes
Physical Properties of the Scrapie Agent
Human TSEs
Hallmarks of TSE Pathogenesis
Prions and the prnp Gene
BOX 13.4. EXPERIMENTS. Detection of Creutzfeldt-Jakob prions in nasal brushings and urine
Prion Strains
BOX 13.5. EXPERIMENTS. Structure of an infectious prion
Bovine Spongiform Encephalopathy
Chronic Wasting Disease
BOX 13.6. EXPERIMENTS. Prions in plants
Treatment of Prion Diseases
Perspectives
REFERENCES. Reviews
Papers of Special Interest
STUDY QUESTIONS
APPENDIX Epidemiology and Pathogenesis of Selected Human Viruses
Adenoviruses
Arenaviruses
Bunyaviruses
Caliciviruses
Coronaviruses
Filoviruses
Flaviviruses
Flaviviruses
Flaviviruses
Hepadnaviruses
Herpesviruses
Herpesviruses
Herpesviruses
Orthomyxoviruses
Papillomaviruses
Paramyxoviruses
Paramyxoviruses
Picornaviruses
Picornaviruses
Picornaviruses
Polyomaviruses
Poxviruses
Reoviruses
Reoviruses
Retroviruses
Retroviruses
Rhabdoviruses
Togaviruses
Togaviruses
Glossary
Index
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