Table of Contents Part I. Introduction 1. A Selective History on the Nature of Viruses Introduction The Early Years: Discoverers and Pioneers The First Stirrings of the Molecular Era The Phage Group Phage Growth: Eclipse and Replication Defining Viruses Are Viruses Alive? Origin of Viruses The Modern Era of Animal Virology 2. Biosynthesis of Viruses: An Introduction to Virus Classification T-Even Bacteriophages as a Model System T-Even Phage Structure and Entry Sequence of Phage Biosynthetic Events Phage Protein Synthesis RNA Metabolism in Infected Cells Assembly of Progeny Phages Packaging DNA within the Phage Particle Unique Features of T-Even Phages Modified Bases Regulated Gene Expression Phage Release: Lysozyme and the rII Region Bacteriophage Lambda: Lysogeny and Transduction Some Final Comments on Bacteriophages Introduction to the Animal Viruses Animal Virus Structure Entry of Animal Viruses The Families of Animal Viruses: Principles of Classification Viral Genetic Systems: The Baltimore Classification Scheme 3. Modes of Virus Infection and Disease Introduction Portals of Entry Routes of Dissemination Hematogenous and Neural Dissemination The Placenta and the Fetus Acute versus Persistent Infections Acute Infections Persistent Infections Slow Infections Chronic Infections Latent Infections Transmissible Spongiform Encephalopathies: Prions 4. Host Defenses and Viral Countermeasures Introduction Overview of Defenses Physical Barriers against Infection The Innate Immune System Cytokines: the Interferons Cytokines: TNF-[alpha], Some Other Cytokines, and Inflammation Macrophages, Neutrophils, and NK Cells and ADCC The Complement System Viral Evasion of Innate Immunity Evasion of Interferons Evasion of Cytokines Evasion of NK Cells and ADCC Evasion of Complement APOBEC3G and the HIV Vif Protein The Adaptive Immune System Antibodies and B Cells Antibody Diversity Viral Evasion of Antibodies Cell-Mediated Immunity Antigen Presentation by MHC Class I Molecules Antigen Presentation by MHC Class II Molecules The Rationale for MHC Restriction Activation of Helper T Cells: Dendritic Cells and B Cells Activation of B Cells Activation of CTLs Mechanism of Action of CTLs T Cells and Antiviral Cytokines Viral Evasion of Cell-Mediated Immunity Inhibition of Antigen Presentation to CTLs Inhibition of Antigen Presentation to Helper T Cells Inhibition of Apoptosis Immunological Memory Self Tolerance The Immune System in Disease Immunopathology Autoimmune Disease Part II. Virus Replication and Pathogenesis subpart RNA Viruses: Double-Stranded 5. Reoviruses Introduction Structure, Binding, Entry, and Uncoating Reovirus Binding and Entry into the Cell Structure, Uncoating, and Entry into the Cytoplasm The Reovirus Genome: Transcription and Translation The Particle-Associated RNA Polymerase The Segmented Reovirus Genome Conversion of ISVPs to Cores Replication and Encapsidation of the Reovirus Genome Synthesis of Double-Stranded RNA Assembly of Progeny Subviral Particles Encapsidation of RNA Segments Reoviruses and Interferon Primary versus Secondary Transcription Final Virus Assembly Pathogenesis Orthoreoviruses Rotaviruses Coltiviruses subpart RNA Viruses: Single-Stranded 6. Picornaviruses Introduction Structure, Binding, and Entry Picornavirus Structure Rhinovirus Receptor and Binding: the Canyon Hypothesis The Poliovirus Receptor Receptors for Coxsackieviruses and Other Enteroviruses Receptors for Foot and Mouth Disease Viruses Poliovirus and Rhinovirus Entry: Some General Points Poliovirus Entry Human Rhinovirus Entry Poliovirus and Rhinovirus Entry: Why the Differences? Translation Translation: Part I Translation: a Digression The RNA Phages Picornaviruses versus RNA Phages: Why the Differences? Translation: Part II Transcription and Genome Replication Assembly and Maturation Medical Aspects Poliovirus Rhinoviruses: the Common Cold Coxsackievirus and Echovirus Viral Hepatitis: Hepatitis A Virus 7. Flaviviruses Introduction Structure and Entry Replication Assembly and Release Historic Interlude: Identification of Hepatitis C Virus West Nile Virus: an Emerging Virus Epidemiology and Pathogenesis General Principles of Arthropod Transmission Infection, Dissemination, and Determinants of Pathogenesis Hemorrhagic Fever Viruses: Yellow Fever and Dengue Encephalitis Viruses: Japanese Encephalitis, St. Louis Encephalitis, and West Nile Viruses Japanese Encephalitis and St. Louis Encephalitis Viruses West Nile Virus Hepatitis C Virus 8. Togaviruses Introduction Structure and Entry Transcription, Translation, and Genome Replication Assembly and Maturation Epidemiology and Pathogenesis Alphaviruses That Cause Encephalitis: Eastern, Western, and Venezuelan Equine Encephalitis Viruses Alphaviruses That Cause Arthritis: Chikungunya, Ross River, and Sindbis Viruses Rubella Virus 9. Coronaviruses Introduction Structure Entry Genome Organization and Expression Coronavirus mRNAs and Their Translation Coronavirus Transcription Coronavirus Recombination Coronavirus Reverse Genetics Assembly and Release Medical Aspects SARS 10. Rhabdoviruses Introduction Structure Entry Genome Organization, Expression, and Replication The General Transcriptional Strategy of Viruses That Contain Negative-Sense RNA Genomes Gene Organization and Transcription Replication Assembly and Release Medical Aspects Cytopathic Effects Vesicular Stomatitis Virus Rabies Virus 11. Paramyxoviruses Introduction Structure Entry Syncytium Formation Genome Organization, Expression, and Replication Genome Organization and Transcription Replication Assembly and Release Medical Aspects Measles Clinical Conditions Sclerosing Panencephalitis (SSPE) Where Did It Come From?