Principles of Virology

Volume I
	Cover
	Title Page
	Copyright Page
	Table of Contents
	Preface
	Acknowledgments
	About the Authors
	Key of Repetitive Elements
	PART I The Science of Virology
		Chapter 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
		Chapter 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
		Chapter 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
		Chapter 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 Structure 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
		Chapter 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 Virus Particles
				Uncoating of Nonenveloped Viruses
			Import of Viral Genomes into the Nucleus
				The Nuclear Pore Complex
				Nuclear Localization Signals
				Nuclear Import of RNA Genomes
				Nuclear Import of DNA Genomes
				Import of Retroviral Genomes
			Perspectives
			References
			Study Questions
		Chapter 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 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
		Chapter 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
		Chapter 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
		Chapter 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
		Chapter 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
		Chapter 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
		Chapter 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
		Chapter 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
		Chapter 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 II
	Cover
	Title Page
	Copyright Page
	Table of Contents
	Preface
	Acknowledgments
	About the Authors
	Key of Repetitive Elements
	Chapter 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
	Chapter 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
	Chapter 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)
			Programmed Necrosis (Necroptosis)
			Autophagy
			Epigenetic Silencing
			Host Proteins That Restrict Virus Reproduction (Restriction Factors)
			RNA Interference
			CRISPR
			The Continuum between Intrinsic and Innate Immunity
		Secreted Mediators of the Innate Immune Response
			Overview of Cytokine Functions
			Interferons, Cytokines of Early Warning and Action
			Chemokines
		The Innate Immune Response
			Monocytes, Macrophages, and Dendritic Cells
			Complement
			Natural Killer Cells
			Other Innate Immune Cells Relevant to Viral Infections
		Perspectives
		References
		Study Questions
	Chapter 4 Adaptive Immunity and 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 Pro cessing 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 CTLs 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 Question Puzzle
	Chapter 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
			Approaches To Identify Viral Genes That Contribute to Virulence
			Viral Virulence Genes
		Pathogenesis
			Infected Cell Lysis
			Immunopathology
			Immunosuppression Induced by Viral Infection
			Oncogenesis
			Molecular Mimicry
		Perspectives
		References
		Study Question Puzzle
	Chapter 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
	Chapter 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
	Chapter 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
	Chapter 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
	Chapter 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
	Chapter 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 Naïve 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
	Chapter 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
			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
		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
		Study Questions
	Chapter 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
EULA