Principles of Virology, Fifth Edition Multi–Volume

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.

Volume 1

Preface


Acknowledgments


About the Authors


PART I: The Science of Virology


1 Foundations


Luria's Credo


Viruses Defined


Why We Study Viruses


Viruses Are Everywhere


Viruses Infect All Living Things


Viruses Can Cause Human Disease


Viruses Can Be Beneficial


Viruses "R" Us


Viruses Can Cross Species Boundaries


Viruses Are Unique Tools To Study Biology


Virus Prehistory


Viral Infections in Antiquity


The First Vaccines Microorganisms as Pathogenic Agents


Discovery of Viruses


The Defining Properties of Viruses


The Structural Simplicity of Virus Particles


The Intracellular Parasitism of Viruses


Cataloging Animal Viruses


The Classical System


Classification by Genome Type: the Baltimore System


A Common Strategy for Viral Propagation


Perspectives


References


Study Questions


2 The Infectious Cycle


Introduction


The Infectious Cycle


The Cell


Entering Cells


Viral RNA Synthesis


Viral Protein Synthesis


Viral Genome Replication


Assembly of Progeny Virus Particles


Viral Pathogenesis


Overcoming Host Defenses


Cultivation of Viruses


Cell Culture


Embryonated Eggs


Laboratory Animals


Assay of Viruses


Measurement of Infectious Units


Efficiency of Plating


Measurement of Virus Particles


Viral Reproduction: the Burst Concept


The One-Step Growth Cycle


One-Step Growth Analysis: a Valuable Tool for Studying Animal Viruses


Global Analysis


DNA Microarrays


Mass Spectrometry


Protein-Protein Interactions


Single-Cell Virology


Perspectives


References


Study Questions


PART II: Molecular Biology


3 Genomes and Genetics


Introduction


Genome Principles and the Baltimore System


Structure and Complexity of Viral Genomes


DNA Genomes


RNA Genomes


What Do Viral Genomes Look Like?


Coding Strategies


What Can Viral Sequences Tell Us?


The "Big and Small" of Viral Genomes: Does Size Matter?


The Origin of Viral Genomes


Genetic Analysis of Viruses


Classical Genetic Methods


Engineering Mutations into Viral Genomes


Engineering Viral Genomes: Viral Vectors


Perspectives


References


Study Questions


4 Structure


Introduction


Functions of the Virion


Nomenclature


Methods for Studying Virus Structure


Building a Protective Coat


Helical Structures


Capsids with Icosahedral Symmetry


Other Capsid Architectures


Packaging the Nucleic Acid Genome


Direct Contact of the Genome with a Protein Shell


Packaging by Specialized Viral Proteins


Packaging by Cellular Proteins


Viruses with Envelopes


Viral Envelope Components


Simple Enveloped Viruses: Direct Contact of External Proteins with the Capsid or Nucleocapsid


Enveloped Viruses with an Additional Protein Layer


Large Viruses with Multiple


Structural Elements Particles with Helical or Icosahedral Parts Alternative Architectures


Other Components of Virions


Enzymes


Other Viral Proteins


Cellular Macromolecules


Mechanical Properties of Virus Particles


Investigation of Mechanical Properties of Virus Particles


Stabilization and Destabilization of Virus Particles


Perspectives


References


Study Questions


5 Attachment and Entry


Introduction


Attachment of Virus Particles to Cells


General Principles


Identification of Receptors for Virus Particles


Virus-Receptor Interactions


Entry into Cells


Virus-induced Signaling via Cell Receptors


Routes of entry


Membrane Fusion


Intracellular Trafficking and Uncoating


Movement of Viral and Subviral Particles within Cells


Uncoating of enveloped viruses


Uncoating of non-enveloped viruses


Import of Viral Genomes into the Nucleus


The Nuclear Pore Complex


Nuclear Localization Signals


Import of RNA Genomes


Import of DNA Genomes


Import of Retroviral Genomes


Perspectives


References


Study Questions


6 Synthesis of RNA from RNA Templates


Introduction


The Nature of the RNA Template


Secondary Structures in Viral RNA


Naked or Nucleocapsid RNA


The RNA Synthesis Machinery


Identification of RNA-Dependent RNA Polymerases


Three-Dimensional Structures of RNA-Dependent RNA Polymerases


Mechanisms of RNA Synthesis


Initiation


Capping


Elongation


Functions of Additional Polymerase Domains


RNA polymerase Oligomerization


Template Specificity


Unwinding the RNA Template


Role of Cellular Proteins


Paradigms for Viral RNA Synthesis


(+) Strand RNA


Synthesis of Nested Subgenomic mRNAs


( ) Strand RNA


Ambisense RNA


Double-Stranded RNA


Unique Mechanisms of mRNA and Genome Synthesis of Hepatitis Delta Satellite Virus


Do Ribosomes and RNA Polymerases Collide?


Origins of Diversity in RNA Virus Genomes


Misincorporation of Nucleotides


Segment Reassortment and RNA Recombination


RNA Editing


Perspectives


References


Study Questions


7 Synthesis of RNA from DNA Templates


Introduction


Properties of Cellular RNA Polymerases That Transcribe Viral DNA


Some Viral Genomes Must Be Converted to Templates Suitable for Transcription


Transcription by RNA Polymerase II


Regulation of RNA Polymerase II Transcription


Common Properties of Proteins That Regulate Transcription


Transcription of Viral DNA Templates by the Cellular Machinery Alone


Viral Proteins That Govern Transcription of DNA Templates


Patterns of Regulation


The Human Immunodeficiency Virus Type 1 Tat Protein Autoregulates Transcription


The Transcriptional Cascades of DNA Viruses


Entry into One of Two Alternative Transcriptional Programs


Transcription of Viral Genes by RNA Polymerase III


The VA-RNA I Promoter


Inhibition of the Cellular Transcriptional Machinery


Unusual Functions of Cellular Transcription Components in Virus-Infected Cells


Viral DNA-Dependent RNA Polymerases


Perspectives


References


Study Questions


8 Processing


Introduction


Covalent Modification during Viral Pre-mRNA Processing


Capping the 5' Ends of Viral mRNA


Synthesis of 3' Poly(A) Segments of Viral mRNA


Internal Methylation of Adenosine Residues


Splicing of Viral Pre-mRNA


Regulated Processing of Viral Pre-mRNA


Editing of Viral mRNAs


Export of RNAs from the Nucleus


The Cellular Export Machinery Export of Viral mRNA


Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins


Temporal Control of Viral Gene Expression


Viral Proteins Can Inhibit Cellular mRNA Production


Regulation of Turnover of Viral and Cellular mRNAs in the Cytoplasm


Intrinsic Turnover


Regulation of mRNA Stability by Viral Proteins


mRNA Stabilization Can Facilitate Transformation


Nonsense-Mediated mRNA Decay


Noncoding RNAs


Small Interfering RNAs and Micro-RNAs


Long Noncoding RNAs


Circular RNAs


Perspectives


References


Study Questions


9 Replication of DNA Genomes


Introduction


DNA Synthesis by the Cellular Replication Machinery


Eukaryotic Replicons


Cellular Replication Proteins


Mechanisms of Viral DNA Synthesis


Lessons from Simian Virus 40


Replication of Other Viral DNA Genomes


Properties of Viral Replication Origins


Recognition of Viral Replication Origins


Viral DNA Synthesis Machines


Resolution and Processing of Viral Replication Products


Exponential Accumulation of Viral Genomes


Viral Proteins Can Induce Synthesis of Cellular Replication Proteins


Synthesis of Viral Replication Machines and Accessory Enzymes


Viral DNA Replication Independent of Cellular Proteins


Delayed Synthesis of Structural Proteins Prevents Premature Packaging of DNA Templates


Inhibition of Cellular DNA Synthesis


Synthesis of Viral DNA in Specialized Intracellular Compartments


Limited Replication of Viral DNA Genomes


Integrated Parvoviral DNA Can Be Replicated as Part of the Cellular Genome


Different Viral Origins Regulate Replication of Epstein-Barr Virus


Limited and Amplifying Replication from a Single Origin: the Papillomaviruses


Origins of Genetic Diversity in DNA Viruses


Fidelity of Replication by Viral DNA Polymerases


Modulation of the DNA Damage Response


Recombination of Viral Genomes


Perspectives


References


Study Questions


10 Reverse Transcription and Integration


Retroviral Reverse Transcription


Discovery


Impact


The Process of Reverse Transcription


General Properties and Structure of Retroviral Reverse Transcriptases


Other Examples of Reverse Transcription


Retroviral DNA Integration


The Pathway of Integration: Integrase-Catalyzed Steps


Integrase Structure and Mechanism


Hepadnaviral Reverse Transcription


A DNA Virus with Reverse Transcriptase


The Process of Hepadnaviral Reverse Transcription


Perspectives


References


Study Questions


11 Protein Synthesis


Introduction


Mechanisms of Eukaryotic Protein Synthesis


General Structure of Eukaryotic mRNA


The Translation Machinery


Initiation


Elongation and Termination


The Diversity of Viral Translation Strategies


Polyprotein Synthesis


Leaky Scanning


Reinitiation


StopGo Translation


Suppression of Termination


Ribosomal Frameshifting


Bicistronic mRNAs


Regulation of Translation during Viral Infection


Inhibition of Translation Initiation after Viral Infection


Regulation of eIF4F


Regulation of Poly(A)-Binding Protein Activity


Regulation of eIF3


Interfering with RNA


Stress-Associated RNA Granules


Perspectives


References


Study Questions


12 Intracellular Trafficking


Introduction


Assembly within the Nucleus


Import of Viral Proteins for Assembly


Assembly at the Plasma Membrane


Transport of Viral Membrane Proteins to the Plasma Membrane


Sorting of Viral Proteins in Polarized Cells


Disruption of the Secretory Pathway in Virus-Infected Cells


Signal Sequence-Independent Transport of Viral Proteins to the Plasma Membrane


Interactions with Internal Cellular Membranes


Localization of Viral Proteins to Compartments of the Secretory Pathway


Localization of Viral Proteins to the Nuclear Membrane


Transport of Viral Genomes to Assembly Sites


Transport of Genomic and Pregenomic RNA from the Nucleus to the Cytoplasm


Transport of Genomes from the Cytoplasm to the Plasma Membrane


Perspectives


References


Study Questions


13 Assembly, Release, and Maturation


Introduction


Methods of Studying Virus Assembly and Egress


Structural Studies of Virus Particles


Visualization of Assembly and Exit by Microscopy


Biochemical and Genetic Analyses of Assembly Intermediates


Methods Based on Recombinant DNA Technology


Assembly of Protein Shells


Formation of Structural Units


Capsid and Nucleocapsid Assembly


Self-Assembly and Assisted Assembly Reactions


Selective Packaging of the Viral Genome and Other Components of Virus Particles


Concerted or Sequential Assembly


Recognition and Packaging of the Nucleic Acid Genome


Incorporation of Enzymes and Other Nonstructural Proteins


Acquisition of an Envelope


Sequential Assembly of Internal Components and Budding from a Cellular Membrane


Coordination of the Assembly of Internal Structures with Acquisition of the Envelope


Release of Virus Particles


Assembly and Budding at the Plasma Membrane


Assembly at Internal Membranes: the Problem of Exocytosis


Release of Nonenveloped Virus Particles


Maturation of Progeny Virus Particles


Proteolytic Processing of Structural Proteins


Other Maturation Reactions


Cell-to-Cell Spread


Perspectives


References


Study Questions


14 The Infected Cell


Introduction


Signal Transduction


Signaling Pathways


Signaling in Virus-Infected Cells


Gene Expression


Inhibition of Cellular Gene Expression


Differential Regulation of Cellular Gene Expression


Metabolism


Methods To Study Metabolism


Glucose Metabolism


The Citric Acid Cycle


Electron Transport and Oxidative Phosphorylation


Lipid Metabolism


Remodeling of Cellular Organelles


The Nucleus


The Cytoplasm


Perspectives


References


Study Questions


APPENDIX Structure, Genome Organization, and Infectious Cycles of Viruses Featured in this Book


Glossary


Index

Volume 2

Preface


Acknowledgments


About the Authors


1 Infections of Populations: History and Epidemiology


Introduction to Viral Pathogenesis


A Brief History of Viral Pathogenesis


The Relationships among Microbes and the Diseases They Cause


The First Human Viruses Identified and the Role of Serendipity


New Methods Facilitate the Study of Viruses as Causes of Disease


Viral Epidemics in History


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


Methods Used by Epidemiologists


Surveillance


Network Theory and Practical Applications


Parameters That Govern the Ability of a Virus to Infect a Population


Geography and Population Density


Climate


Perspectives


References


Study Questions


2 Barriers to Infection


Introduction


An Overview of Infection and Immunity


A Game of Chess Played by Masters


Initiating an Infection


Successful Infections Must Modulate or Bypass Host Defenses


Skin


Respiratory Tract


Alimentary Tract


Eyes


Urogenital Tract


Placenta


Viral Tropism


Accessibility of Viral Receptors


Other Host-Virus Interactions That Regulate the Infectious Cycle


Spread throughout the Host


Hematogenous Spread


Neural Spread


Organ Invasion


Entry into Organs with Sinusoids


Entry into Organs That Lack Sinusoids


Organs with Dense Basement Membranes


Skin


Shedding of Virus Particles


Respiratory Secretions


Saliva


Feces


Blood


Urine


Semen


Milk


Skin Lesions


Tears


Perspectives


References


Study Questions


3 The Early Host Response: Cell Autonomous and Innate Immunity


Introduction


The First Critical Moments: How Do Individual Cells Detect a Virus Infection?


Cell Signaling Induced by Viral Entry Receptor Engagement


Receptor-Mediated Recognition of Microbe-Associated Molecular Patterns


Cell Intrinsic Defenses


Apoptosis (Programmed Cell Death)


Necroptosis and Other Cell Death Pathways


Autophagy


Epigenetic Silencing


Cellular Restriction Factors


RNA Interference


CRISPR


The Continuum Between Intrinsic and Innate Immunity


Secreted Immune Mediators of the Innate Immune Response


Overview of Cytokine Functions


Interferons, Cytokines of Early Warning and Action


Chemokines


The Innate Immune Response


Monocytes/macrophages


Complement


Natural Killer Cells


Innate Lymphoid Cells


Other Innate Immune Cells of Relevance to Viral Infections


Perspectives


References


Study Questions


4 Adaptive Immunity and the Establishment of Memory


Introduction


Attributes of the Host Response


Speed


Diversity and Specificity


Memory


Self-Control


Lymphocyte Development, Diversity, and Activation


The Hematopoietic Stem Cell Lineage


The Two Arms of Adaptive Immunity


The Major Effectors of the Adaptive Response: B and T Cells


Diverse Receptors Impart Antigen Specificity to B and T Cells


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


Activated Antigen-Presenting Cells Leave the Site of Infection and Migrate to Lymph Nodes


Antigen Processing and Presentation


Professional Antigen-Presenting Cells Induce Activation via Costimulation


Presentation of Antigens by Class I and Class II MHC Proteins


Lymphocyte Activation Triggers Massive Cell Proliferation


The CTL (Cell-Mediated) Response


CTLs Lyse Virus-Infected Cells


Control of CTL Proliferation


Control of Infection by T Cells without Killing


Rashes and Poxes


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


Study Questions


5 Patterns and Pathogenesis


Introduction


Animal Models of Human Diseases


Patterns of Infection


Incubation Periods


Mathematics of Growth Correlate with Patterns of Infection


Acute Infections


Persistent Infections


Latent Infections


Abortive Infections


Transforming Infections


Viral Virulence


Measuring Viral Virulence


Alteration of Viral Virulence


Viral Virulence Genes


Pathogenesis


Infected Cell Lysis


Immunopathology


Immunosuppression Induced by Viral Infection


Oncogenesis


Molecular Mimicry


Perspectives


References


Study Questions


6 Cellular Transformation and Oncogenesis


Introduction


Properties of Transformed Cells


Control of Cell Proliferation


Oncogenic Viruses


Discovery of Oncogenic Viruses


Viral Genetic Information in Transformed Cells


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


Alteration of the Production or Activity of Cellular Signal Transduction Proteins


Disruption of Cell Cycle Control Pathways by Viral Transforming Proteins


Abrogation of Restriction Point Control Exerted by the RB Protein


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


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


Perspectives


References


Study Questions


7 Vaccines


Introduction


The Origins of Vaccination


Smallpox: a Historical Perspective


Worldwide Vaccination Programs Can Be Dramatically Effective


Vaccine Basics


Immunization Can Be Active or Passive


Active Vaccination Strategies Stimulate Immune Memory


The Fundamental Challenge


The Science and Art of Making Vaccines


Inactivated Virus Vaccines


Attenuated Virus Vaccines


Subunit Vaccines


Virus-Like Particles


Nucleic Acid Vaccines


Vaccine Technology: Delivery and Improving Antigenicity


Adjuvants Stimulate an Immune Response


Delivery and Formulation


Immunotherapy


The Ongoing Quest for an AIDS Vaccine


Perspectives


References


Study Question Puzzle


8 Antiviral Drugs


Introduction


A Brief History of Antiviral Drug Discovery


Discovering Antiviral Compounds


The Lexicon of Antiviral Discovery


Screening for Antiviral Compounds


Computational Approaches to Drug Discovery


The Difference between "R" and "D"


Drug Resistance


Examples of Antiviral Drugs


Inhibitors of Virus Attachment and Entry


Inhibitors of Viral Nucleic Acid Synthesis


Inhibition of Viral Polyprotein Processing and Assembly


Inhibition of Virus Particle Release


Expanding Targets for Antiviral Drug Development


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


Challenges Remaining


Perspectives


References


Study Questions


9 Therapeutic Viruses


Introduction


Phage Therapy


History


Some Advantages and Limitations of Phage Therapy


Applications in the Clinic and for Disease Prevention


Future Prospects


Oncolytic Animal Viruses


From Anecdotal Reports to Controlled Clinical Trials


Rational Design of Oncolytic Viruses


Two Clinically Approved Oncolytic Viruses


Future Directions


Gene Therapy


Introduction


Retroviral Vectors


Adenovirus-Associated Virus Vectors


Future Prospects


Vaccine Vectors


DNA Viruses


RNA Viruses


Perspectives


References


Study Questions


10 Virus Evolution


Virus Evolution


How Do Virus Populations Evolve?


Two General Virus Survival Strategies Can Be Distinguished


Large Numbers of Viral Progeny and Mutants Are Produced in Infected Cells


The Quasispecies Concept


Genetic Shift and Genetic Drift


Fundamental Properties of Viruses That Constrain Evolution


Two General Pathways for Virus Evolution


Evolution of Virulence


The Origin of Viruses


When and How Did They Arise?


Evolution of Contemporary Eukaryotic Viruses


Host-Virus Relationships Drive Evolution


DNA Virus-Host Relationships


RNA Virus-Host Relationships


The Host-Virus "Arms Race"


Lessons from Paleovirology


Endogenous Retroviruses


DNA Fossils Derived from Other RNA Viral Genomes


Endogenous Sequences from DNA Viruses


Short- versus Long-Term Rates of Viral Evolution


Perspectives


References


Study Questions


11 Emergence


The Spectrum of Host-Virus Interactions


Stable Interactions


The Evolving Host-Virus Interaction


The Dead-End Interaction


The Resistant Host


Encountering New Hosts: Humans Constantly Provide New Venues for Infection


Common Sources for Animal-to-Human Transmission


Viral Diseases That Illustrate the Drivers of Emergence


Poliomyelitis: Unexpected Consequences of Modern Sanitation


Introduction of Viruses into Naive Populations


Hantavirus Pulmonary Syndrome: Changing Animal Populations


Severe Acute and Middle East Respiratory Syndromes (SARS and MERS): Zoonotic Coronavirus Infections


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


A Revolution in Virus Discovery


Perceptions and Possibilities


Virus Names Can Be Misleading


All Viruses Are Important


Can We Predict the Next Viral Pandemic?


Preventing Emerging Virus Infections


Perspectives


References


Study Questions


12 Human Immunodeficiency Virus Type I Pathogenesis


Introduction


Worldwide Impact of AIDS


HIV-1 Is a Lentivirus


Discovery and Characterization


Distinctive Features of the HIV-1 Reproduction Cycle and the Functions of HIV-1 Proteins


The Viral Capsid Counters Intrinsic Defense Mechanisms


Entry and Transmission


Entry in the Cell


Entry into the Body


Transmissions 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


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


Confronting the Problems of Persistence and Latency


Gene Therapy Approaches


Immune System-Based Therapies


Antiviral Drug Prophylaxis


Perspectives


References


13 Unusual Infectious Agents


Introduction


Viroids


Replication


Sequence Diversity


Movement


Pathogenesis


Satellite Viruses and RNAs


Replication


Pathogenesis


Hepatitis Delta Virus


Prions and Transmissible Spongiform Encephalopathies


Scrapie


Physical Properties of the Scrapie Agent


Human TSEs


Hallmarks of TSE Pathogenesis


Prions and the prnp Gene


Prion Strains


Bovine Spongiform Encephalopathy


Chronic Wasting Disease


Treatment of Prion Diseases


Perspectives


References


Study Questions


APPENDIX Epidemiology and Pathogenesis of Selected Human Viruses


Glossary


Index