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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 understand 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.

Principles of Virology, Fifth Edition Multi-Volume

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