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?
Measles Vaccine
Mumps
Parainfluenza Viruses
Respiratory Syncytial Virus
Human Metapneumovirus
Hendra, Nipah, and Menangle Viruses
Canine Distemper Virus
12. Orthomyxoviruses
Introduction
Structure
Entry
Endocytosis and Intracellular Trafficking of Virus-Containing Endosomes
Viral Membrane Fusion: the HA Protein
Release of the Genome from the Envelope: the M2 Protein
Transport of vRNPS to the Cell Nucleus
Genome Organization, Transcription, and Replication
Genome Organization and Transcription
Why Does Influenza Virus Transcription Really Occur in the Nucleus?
Replication
The NS1 and PB1-F2 Proteins
Assembly and Release
Assembly of vRNPs
Two Issues Regarding Intracellular Targeting of Viral Components
Transport of vRNPs from Nucleus to Cytoplasm
Apical Targeting of Virus Components and Final Virus Assembly
Encapsidating Eight Distinct Genomic Segments
Release: the Influenza Virus NA Protein
Medical Aspects
Pathology and Clinical Syndromes
The Flu Pandemic of 1918
Origin of Epidemic and Pandemic Strains: Antigenic Drift and Antigenic Shift
Virulence of the 1918 Pandemic Influenza Virus: Opening Pandora’s Box
Influenza Drugs and Vaccines
Avian Influenza and Humans
Preparedness for an Outbreak of Avian Influenza
13. Miscellaneous RNA Viruses
Introduction
Arenaviruses
Lassa Fever Virus: an Early Emerging Virus
LCMV and Immunopathology
The Ambisense Arenavirus Genomes
Bunyaviruses
Sin Nombre and Haantan Viruses
The Tripartite Bunyavirus Genomes
Bornaviruses
BDV and Human Neuropsychiatric Disease
Bornavirus Genomes and Their Nuclear Transcription and Replication
Caliciviruses
Norwalk Virus
Calicivirus Replication
Astroviruses
Hepatitis E-Like Viruses
Filoviruses
Structure and Replication
Marburg and Ebola Viruses
Is Ebola Virus the “Andromeda Strain?”
subpart DNA Viruses: Single-Stranded
14. Parvoviruses
Introduction
Parvovirus Structure, Binding, and Entry
Parvovirus Genomes
Replication of Parvovirus Single-Stranded DNA
A General Model: the “Rolling Hairpin”
Encapsidation of Progeny DNA
Genome Organization and Expression
The Dependovirus Life Cycle
Integration of Dependovirus Genomes
Medical Aspects
subpart DNA Viruses: Double-Stranded
15. Polyomaviruses
Introduction
Structure
Entry and Uncoating
Genome Organization and Expression
Genome Organization
The Regulatory Region
T Antigen in Temporal Regulation of Transcription
Splicing Pattern of Viral mRNA
DNA Replication
Late Proteins and Assembly
T Antigens and Neoplasia
SV40 in Its Natural Host
SV40 in Humans
JC-V and BK-V in Humans
Ki, Wu, and Merkel Cell Human Polyomaviruses
SV40-Based Gene Delivery Vectors
16. Papillomaviruses
Introduction
Structure
Entry and Uncoating
Genome Organization and Expression
Replication
Release and Transmission
Cell Transformation and Oncogenesis: Cervical Carcinoma
Treatment and Prevention
HPV Vaccine To Prevent Cervical Cancer
17. Adenoviruses
Introduction
Structure
Entry and Uncoating
Genome Organization and Expression
E1A and E1B Proteins in Replication and Neoplasia
Shutoff of Host Protein Synthesis
DNA Replication
Assembly
Evasion of Host Defenses
Clinical Syndromes
Recombinant Adenoviruses
Gene Therapy
Cancer Therapies
Vaccines: HIV and Influenza
18. Herpesviruses
Introduction
Structure
Entry and Uncoating
Genome Organization and Expression
DNA Replication
Assembly, Maturation, and Release
Assembly of Procapsids
Encapsidation of DNA
Final Assembly and Release
Latent Infection and Immune Evasion
Herpes Simplex Virus
Epstein-Barr Virus
Human Cytomegalovirus
Clinical Syndromes
HSV
EBV
HCMV
VZV
HHV--6
HHV--7
HHV--8
Treatment and Prevention
Antiviral Drugs
Vaccines
19. Poxviruses
Introduction
Structure