Оглавление
Jane Flint. Principles of Virology, Volume 1
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
VOLUME I Molecular Biology. PRINCIPLES OF. Virology
About the Instructor Companion Website
Preface
What’s New
Principles Taught in Two Distinct, but Integrated Volumes
Volume I: The Science of Virology and the Molecular Biology of Viruses
Volume II: Pathogenesis, Control, and Evolution
Acknowledgments
About the Authors
Key of Repetitive Elements
PART I The Science of Virology
1 Foundations
LINKS FOR CHAPTER 1
Luria’s Credo
Viruses Defined
Why We Study Viruses. Viruses Are Everywhere
PRINCIPLES Foundations
Viruses Infect All Living Things
BOX 1.1. BACKGROUND. Some astounding numbers
BOX 1.2. DISCUSSION. The first animal virus discovered remains a scourge today
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
BOX 1.3. DISCUSSION. Origin of vaccinia virus
Discovery of Viruses
BOX 1.4. DISCUSSION. New methods amend Koch’s principles
The Defining Properties of Viruses
The Structural Simplicity of Virus Particles
The Intracellular Parasitism of Viruses. Organisms as Hosts
Lessons from Bacteriophages
Animal Cells as Hosts
BOX 1.5. EXPERIMENTS. The Hershey-Chase experiment
BOX 1.6. BACKGROUND. Properties of lysogeny shared with animal viruses. Lytic versus Lysogenic Response to Infection
Propagation as a Prophage
Insertional Mutagenesis
Gene Repression and Induction
Transduction of Host Genes
BOX 1.7. TERMINOLOGY. The episome
BOX 1.8. DISCUSSION. Are viruses living entities? What can/can’t they do?
Cataloging Animal Viruses
The Classical System
BOX 1.9. TERMINOLOGY. Complexities of viral nomenclature
Classification by Genome Type: the Baltimore System
BOX 1.10. DISCUSSION. Giant viruses discovered in amoebae
A Common Strategy for Viral Propagation
Perspectives
REFERENCES. Books
STUDY QUESTIONS
2 The Infectious Cycle
LINKS FOR CHAPTER 2
Introduction
The Infectious Cycle
The Cell
PRINCIPLES The infectious cycle
Entering Cells
Viral RNA Synthesis
Viral Protein Synthesis
Viral Genome Replication
Assembly of Progeny Virus Particles
Viral Pathogenesis
BOX 2.1. EXPERIMENTS. In vitro assembly of tobacco mosaic virus
Overcoming Host Defenses
Cultivation of Viruses. Cell Culture. Types of Cell Culture
BOX 2.2. BACKGROUND. The cells of Henrietta Lacks
BOX 2.3. EXPERIMENTS. Zika virus blocks the neuronal road
Evidence of Viral Reproduction in Cultured Cells
BOX 2.4. TERMINOLOGY. In vitro and in vivo
Embryonated Eggs
Laboratory Animals
Assay of Viruses
Measurement of Infectious Units
Plaque Assay
Fluorescent-Focus Assay
BOX 2.5. METHODS. Calculating virus titer from the plaque assay
Infectious-Centers Assay
Transformation Assay
End-Point Dilution Assay
Efficiency of Plating
BOX 2.6. METHODS. End-point dilution assays
Measurement of Virus Particles
Electron Microscopy
Hemagglutination
Centrifugation
Measurement of Viral Enzyme Activity
Serological Methods
BOX 2.7. DISCUSSION. Neutralization antigenic sites
Fluorescent Proteins
Fluorescence Microscopy
Detection of Viral Nucleic Acids
BOX 2.8. EXPERIMENTS. Viral RNA is not infectious virus
BOX 2.9. EXPERIMENTS. Pathogen de-discovery
Viral Reproduction: the Burst Concept
The One-Step Growth Cycle
BOX 2.10. METHODS. How to read a phylogenetic tree
One-Step Growth Analysis: a Valuable Tool for Studying Animal Viruses
BOX 2.11. DISCUSSION. Multiplicity of infection (MOI)
Global Analysis
DNA Microarrays
Mass Spectrometry
Protein-Protein Interactions
Single-Cell Virology
BOX 2.12. WARNING. Determining a role for cellular proteins in viral reproduction can be quite difficult
Perspectives
REFERENCES. Books
Review Articles
Papers of Special Interest
STUDY QUESTIONS
PART II Molecular Biology
3 Genomes and Genetics
LINKS FOR CHAPTER 3
Introduction
Genome Principles and the Baltimore System
Structure and Complexity of Viral Genomes
PRINCIPLES Genomes and Genetics
BOX 3.1. BACKGROUND. What information is encoded in a viral genome?
BOX 3.2. TERMINOLOGY. Important conventions: plus (+) and minus (–) strands
DNA Genomes
Double-Stranded DNA (dsDNA) (Fig. 3.2)
Gapped DNA (Fig. 3.3)
Single-Stranded DNA (ssDNA) (Fig. 3.4)
RNA Genomes
dsRNA (Fig. 3.5)
BOX 3.3. BACKGROUND. RNA synthesis in cells
(+) Strand RNA (Fig. 3.6)
(+) Strand RNA with a DNA Intermediate (Fig. 3.7)
(–) Strand RNA (Fig. 3.8)
What Do Viral Genomes Look Like?
Coding Strategies
What Can Viral Sequences Tell Us?
The “Big and Small” of Viral Genomes: Does Size Matter?
BOX 3.4. EXPERIMENTS. Planaria and mollusks yield the biggest RNA genomes
The Origin of Viral Genomes
Genetic Analysis of Viruses
BOX 3.5. EXPERIMENTS. Origin of segmented RNA virus genomes
Classical Genetic Methods. Mapping Mutations
Functional Analysis
BOX 3.6. METHODS. Spontaneous and induced mutations
BOX 3.7. TERMINOLOGY. What is wild type?
Engineering Mutations into Viral Genomes. Infectious DNA Clones
BOX 3.8. TERMINOLOGY. DNA-mediated transformation and transfection
BOX 3.9. METHODS. Synthesis of infectious horsepox virus from chemically synthesized DNA
Types of Mutation
Introducing Mutations into the Viral Genome
Reversion Analysis
BOX 3.10. TERMINOLOGY. Operations on nucleic acids and proteins
BOX 3.11. DISCUSSION. Is the observed phenotype due to the mutation?
RNA Interference (RNAi)
Targeted Gene Editing with CRISPR-Cas9
Haploid Cell Screening
Engineering Viral Genomes: Viral Vectors
DNA Virus Vectors
RNA Virus Vectors
Perspectives
REFERENCES. Review Articles
Papers of Special Interest
STUDY QUESTIONS
4 Structure
LINKS FOR CHAPTER 4
Introduction
Functions of the Virion
PRINCIPLES Structure
Nomenclature
Methods for Studying Virus Structure
BOX 4.1. METHODS. The development of cryo-electron microscopy, a revolution in structural biology
Building a Protective Coat
Helical Structures
BOX 4.2. METHODS. Nanoconstruction with virus particles
Capsids with Icosahedral Symmetry. General Principles
BOX 4.3. BACKGROUND. The triangulation number, T, and how it is determined
BOX 4.4. EXPERIMENTS. Viral chain mail: not the electronic kind
Structurally Simple Capsids
BOX 4.5. DISCUSSION. Remarkable architectural relationships among viruses with double-stranded DNA genomes
Structurally Sophisticated Capsids
BOX 4.6. EXPERIMENTS. A fullerene cone model of the human immunodeficiency virus type 1 capsid
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
BOX 4.7. EXPERIMENTS. A high-resolution view of an encapsidated viral genome
Viruses with Envelopes
Viral Envelope Components
Envelope Glycoproteins
BOX 4.8. DISCUSSION. A viral membrane directly surrounding the genome
Other Envelope Proteins
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
BOX 4.9. DISCUSSION. A virus particle with different structures in different hosts
Particles with Helical or Icosahedral Parts. Bacteriophage T4
BOX 4.10. DISCUSSION. The extreme pleomorphism of influenza A virus, a genetically determined trait of unknown function
Herpesviruses
Mimiviruses
Alternative Architectures
Poxviruses
Pithoviruses
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. Reviews
Papers of Special Interest
Websites
STUDY QUESTIONS
5 Attachment and Entry
LINKS FOR CHAPTER 5
Introduction
Attachment of Virus Particles to Cells. General Principles
PRINCIPLES Attachment and entry
BOX 5.1. TERMINOLOGY. Is it a receptor or a coreceptor?
Identification of Receptors for Virus Particles
Virus-Receptor Interactions
Nonenveloped Virus Receptor Binding
Alternative Attachment Strategies
Transmembrane Glycoproteins of Enveloped Viruses Mediate Attachment and Entry
Cell Surface Lectins and Spread of Infection
Entry into Cells
Virus-Induced Signaling via Cell Receptors
Routes of Entry
Membrane Fusion
Class I Fusion Proteins
Alternative Fusion Triggers
BOX 5.2. BACKGROUND. Unusual triggers of retroviral fusion proteins
The Membrane Fusion Process
Class II Fusion Proteins
BOX 5.3. EXPERIMENTS. Membrane fusion proceeds through a hemifusion intermediate
BOX 5.4. DISCUSSION. Sex and the fusion protein
Class III Fusion Proteins
Intracellular Trafficking and Uncoating
Movement of Viral and Subviral Particles within Cells
Uncoating of Enveloped Virus Particles. Release of Viral Ribonucleoprotein
Uncoating by Ribosomes in the Cytoplasm
Uncoating of Nonenveloped Viruses. Disrupting the Endosomal Membrane
Forming a Pore in the Endosomal Membrane
Disrupting the Lysosomal Membrane
Import of Viral Genomes into the Nucleus
The Nuclear Pore Complex
Nuclear Localization Signals
Nuclear Import of RNA Genomes
BOX 5.5. BACKGROUND. Transport through the nuclear pore
Nuclear Import of DNA Genomes
Import of Retroviral Genomes
BOX 5.6. DISCUSSION. The bacteriophage DNA injection machine
Perspectives
REFERENCES. Books
Reviews
Papers of Special Interest
STUDY QUESTIONS
6 Synthesis of RNA from RNA Templates
LINKS FOR CHAPTER 6
Introduction
The Nature of the RNA Template. Secondary Structures in Viral RNA
PRINCIPLES Synthesis of RNA from RNA templates
BOX 6.1. TERMINOLOGY. What should we call RNA polymerases and the processes they catalyze?
Naked or Nucleocapsid RNA
The RNA Synthesis Machinery. Identification of RNA-Dependent RNA Polymerases
Three-Dimensional Structures of RNA-Dependent RNA Polymerases
BOX 6.2. BACKGROUND. Two-metal mechanism of catalysis by polymerases
Mechanisms of RNA Synthesis. Initiation
De Novo Initiation
Primer-Dependent 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
BOX 6.3. EXPERIMENTS. Mapping gene order by UV irradiation
Ambisense RNA
Double-Stranded RNA
Unique Mechanisms of mRNA and Genome Synthesis of Hepatitis Delta Virus
BOX 6.4. EXPERIMENTS. Release of mRNA from rotavirus particles
BOX 6.5. BACKGROUND. Ribozymes
Do Ribosomes and RNA Polymerases Collide?
Origins of Diversity in RNA Virus Genomes. Misincorporation of Nucleotides
Segment Reassortment and RNA Recombination
RNA Editing
BOX 6.6. DISCUSSION. RNA recombination leading to the production of pathogenic viruses
Perspectives
REFERENCES. Reviews
Papers of Special Interest
STUDY QUESTIONS
7 Synthesis of RNA from DNA Templates
LINKS FOR CHAPTER 7
Introduction
Properties of Cellular RNA Polymerases That Transcribe Viral DNA. Eukaryotes Have Three Transcriptional Systems
PRINCIPLES Synthesis of RNA from DNA templates
Cellular RNA Polymerases II and III Transcribe Viral Templates
Some Viral Genomes Must Be Converted to Templates Suitable for Transcription
Transcription by RNA Polymerase II
BOX 7.1. EXPERIMENTS. Mapping of a human adenovirus type 2 initiation site and accurate transcription in vitro
Regulation of RNA Polymerase II Transcription
Recognition of Local and Distant Regulatory Sequences
The Simian Virus 40 Enhancer: a Model for Viral and Cellular Enhancers
BOX 7.2. TERMINOLOGY. The idiosyncratic nomenclature for sequence-specific DNA-binding proteins that regulate transcription
BOX 7.3. DISCUSSION. Host cell metabolism can regulate viral enhancers
Common Properties of Proteins That Regulate Transcription
BOX 7.4. EXPERIMENTS. Mechanisms of enhancer action
Transcription of Viral DNA Templates by the Cellular Machinery Alone
Viral Proteins That Govern Transcription of DNA Templates. Patterns of Regulation
BOX 7.5. EXPERIMENTS. Epigenetic silencing of integrated proviral DNAs
The Human Immunodeficiency Virus Type 1 Tat Protein Autoregulates Transcription
Cellular Proteins Recognize the HIV-1 LTR
The Tat Protein Regulates Transcription by Unique Mechanisms
BOX 7.6. WARNING. Caution: transient-expression assays do not reproduce conditions within virus-infected cells
The Transcriptional Cascades of DNA Viruses. Common Strategies Are Executed by Virus-Specific Mechanisms
Examples of Viral Proteins That Stimulate Transcription
BOX 7.7. EXPERIMENTS. In vivo functions of the VP16 acidic activation domain
Coordination of Transcription of Late Genes with Viral DNA Synthesis
BOX 7.8. DISCUSSION. Some potential advantages of temporal regulation of viral gene expression
Entry into One of Two Alternative Transcriptional Programs
BOX 7.9. EXPERIMENTS. Coupling productive transcription of herpes simplex virus late genes to establishment of viral replication forks
BOX 7.10. DISCUSSION. Two bacteriophage lambda repressors govern the outcome of infection
Transcription of Viral Genes by RNA Polymerase III
BOX 7.11. EXPERIMENTS. Partial reversal of repressive histone modification during reactivation of herpes simplex virus type 1 (HSV-1) from latency
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. Reviews
Papers of Special Interest
STUDY QUESTIONS
8 Processing
LINKS FOR CHAPTER 8
Introduction
PRINCIPLES Processing
Covalent Modification during Viral Pre-mRNA Processing. Capping the 5′ Ends of Viral mRNA
Synthesis of Viral 5′ Cap Structures by Cellular Enzymes
BOX 8.1. TRAILBLAZER. Identification of 5′ cap structures on viral mRNAs
Synthesis of Viral 5′ Cap Structures by Viral Enzymes
Acquisition of Viral 5′ Cap Structures from Cellular RNAs
Synthesis of 3′ Poly(A) Segments of Viral mRNA
Polyadenylation of Viral Pre-mRNA by Cellular Enzymes
BOX 8.2. TRAILBLAZER. Identification of poly(A) sequences on viral mRNAs
Polyadenylation of Viral Pre-mRNAs by Viral Enzymes
Internal Methylation of Adenosine Residues. Discovery of Internal Methylation
Stimulation of Viral mRNA Production and Translation
Inhibition of Virus Reproduction
Splicing of Viral Pre-mRNA. Discovery of Splicing
BOX 8.3. TRAILBLAZER. Discovery of the spliced structure of adenoviral major late mRNAs
Mechanism of Splicing
Alternative Splicing
Regulated Processing of Viral Pre-mRNA
BOX 8.4. DISCUSSION. Catalysis of pre-mRNA splicing by RNA
Cellular Differentiation Regulates Production of Papillomaviral Late Pre-mRNAs
Production of Spliced and Unspliced RNAs Essential for Virus Reproduction
Temporal Regulation of Synthesis of Adenoviral Major Late mRNAs
Editing of Viral mRNAs
Editing during mRNA Synthesis
Editing following mRNA Synthesis
BOX 8.5. EXPERIMENTS. RNA editing regulates the cytotoxicity of Ebola viruses
Export of RNAs from the Nucleus
The Cellular Export Machinery
Export of Viral mRNA
The Human Immunodeficiency Virus Type 1 Rev Protein Directs Export of Intron-Containing mRNAs
RNA Signals Can Mediate Export of intron-containing Viral mRNAs by Cellular Proteins
Export of Unspliced Viral mRNAs
BOX 8.6. METHODS. Increasing expression of transgenes in mammalian cells using the woodchuck hepatitis virus posttranscriptional regulatory element
Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins
Temporal Control of Viral Gene Expression. Regulation of Alternative Splicing and Polyadenylation by Viral Proteins
BOX 8.7. EXPERIMENTS. A single adenoviral protein controls the early-to-late switch in major late RNA processing
Regulation of mRNA Export
Viral Proteins Can Inhibit Cellular mRNA Production
Inhibition of Polyadenylation and Splicing
Inhibition of Cellular mRNA Export
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
BOX 8.8. DISCUSSION. Coopting a cellular mechanism of RNA degradation leads to viral pathogenesis
BOX 8.9. DISCUSSION. No longer an oddity of herpesviruses: splicing-related noncoding RNAs
Noncoding RNAs
Small Interfering RNAs and Micro-RNAs. Discovery and Synthesis
Cellular miRNAs in Virus-Infected Cells
Viral Micro-RNAs
BOX 8.10. DISCUSSION. A cellular miRNA that protects the hepatitis C virus genome from degradation and promotes its replication
Viral Gene Products That Block RNA Interference
Long Noncoding RNAs
Cellular lncRNAs in Infected Cells
Cellular lncRNAs That Modulate Virus Reproduction
Viral lncRNAs
Circular RNAs
Perspectives
BOX 8.11. EXPERIMENTS. An unusual viral circular RNA, both coding and linked to oncogenesis
REFERENCES. Reviews
Papers of Special Interest
STUDY QUESTIONS
9 Replication of DNA Genomes
LINKS FOR CHAPTER 9
Introduction
PRINCIPLES Replication of DNA genomes
DNA Synthesis by the Cellular Replication Machinery
Eukaryotic Replicons. General Features
BOX 9.1. EXPERIMENTS. Discoveries of primer-independent DNA polymerases: another dogma overturned
BOX 9.2. BACKGROUND. The two mechanisms of synthesis of double-stranded viral DNA molecules
Origins of Cellular Replication
Cellular Replication Proteins. Eukaryotic DNA Polymerases
Other Proteins Required for DNA Synthesis in Mammalian Cells
Mechanisms of Viral DNA Synthesis
Lessons from Simian Virus 40. The Origin of SV40 DNA Replication
Mechanism of SV40 DNA Synthesis
BOX 9.3. EXPERIMENTS. Mapping of the simian virus 40 origin of replication
Replication of Other Viral DNA Genomes
Synthesis of Viral RNA Primers by Cellular or Viral Enzymes
Priming via DNA: Specialized Structures in Viral Genomes
BOX 9.4. EXPERIMENTS. Unwinding of the simian virus 40 origin leads to spooling of DNA
Protein Priming
Properties of Viral Replication Origins
Number of Origins
Viral Replication Origins Share Common Features
BOX 9.5. BACKGROUND. Rolling-circle replication
Recognition of Viral Replication Origins
Properties of Simian Virus 40 LT
Viral Origin Recognition Proteins Share Several Properties
BOX 9.6. EXPERIMENTS. The mechanism by which simian virus 40 LT unwinds and translocates along DNA
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
Functional Inactivation of the RB Protein
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
BOX 9.7. DISCUSSION. Are viral replication foci a universal feature of cells infected by DNA viruses?
Limited Replication of Viral DNA Genomes
Integrated Parvoviral DNA Can Be Replicated as Part of the Cellular Genome
BOX 9.8. BACKGROUND. Ubiquitinylation of proteins
Different Viral Origins Regulate Replication of Epstein-Barr Virus
BOX 9.9. DISCUSSION. Integration into host cell telomeres as a mechanism of herpesvirus latency?
Limited and Amplifying Replication from a Single Origin: the Papillomaviruses
BOX 9.10. EXPERIMENTS. Distinguishing once-per-cell-cycle from random replication of human papillomavirus DNA
Origins of Genetic Diversity in DNA Viruses. Fidelity of Replication by Viral DNA Polymerases. Proofreading Mechanisms
Proofreading by Viral DNA Polymerases
Modulation of the DNA Damage Response
Inhibition of DNA Damage Responses
Differential Impacts on DNA Damage Response Pathways
DNA Damage Responses Essential for Virus Reproduction
Recombination of Viral Genomes. General Mechanisms of Recombination
Origin-Independent, Recombination-Dependent Replication
Viral Genome Recombination
BOX 9.11. DISCUSSION. Replication and recombination/repair are two sides of the same coin: earliest insights from bacteriophage λ
Perspectives
REFERENCES. Reviews
Papers of Special Interest
STUDY QUESTIONS
10 Reverse Transcription and Integration
LINKS FOR CHAPTER 10
Retroviral Reverse Transcription. Discovery
Impact
PRINCIPLES Reverse transcription and integration
BOX 10.1. TRAILBLAZER. Bacteriophage lambda, a paradigm for the joining of retroviral and host DNAs
The Process of Reverse Transcription
Essential Components
BOX 10.2. TERMINOLOGY. Conventions for designating sequences in nucleic acids
BOX 10.3. DISCUSSION. tRNA mimicry and the primer-binding site of human immunodeficiency virus type 1 (HIV-1) genomic RNA
Distinct Steps in Reverse Transcription
BOX 10.4. WARNING
General Properties and Structure of Retroviral Reverse Transcriptases. Domain Structure and Variable Subunit Organization
Catalytic Properties
Structure of RT
Other Examples of Reverse Transcription
BOX 10.5. DISCUSSION. Reverse transcriptase can reverse direction
BOX 10.6. BACKGROUND. Present-day establishment of endogenous retroviruses—a race against time?
Retroviral DNA Integration
The Pathway of Integration: Integrase-Catalyzed Steps
BOX 10.7. BACKGROUND. Model in vitro reactions elucidate catalytic mechanisms of retroviral integrase
Multiple Parameters Govern Selection of Host DNA Target Sites
Other Host Proteins May Affect Integration
Integrase Structure and Mechanism. IN Proteins Are Composed of Three Structural Domains
A Multimeric Form of IN Is Required for Catalysis
Characterization of Intasomes
Hepadnaviral Reverse Transcription. A DNA Virus with Reverse Transcriptase
BOX 10.8. DISCUSSION. A retrovirus with a DNA genome?
Reverse Transcription in the Hepadnaviral Infectious Cycle
The Process of Hepadnaviral Reverse Transcription. Essential Components
Critical Steps in Reverse Transcription
BOX 10.9. DISCUSSION. A single P-protein molecule does it all?
Perspectives
REFERENCES. Books
Landmark Publications and Papers of Special Interest
Hepadnaviral Reverse Transcription
STUDY QUESTIONS
11 Protein Synthesis
LINKS FOR CHAPTER 11
Introduction
Mechanisms of Eukaryotic Protein Synthesis. General Structure of Eukaryotic mRNA
PRINCIPLES Protein synthesis
BOX 11.1. TRAILBLAZER. Viral components of the translational machinery
The Translation Machinery. Ribosomes
tRNAs
Translation Proteins
Initiation
5′-End-Dependent Initiation
5′-End-Independent Initiation
BOX 11.2. TRAILBLAZER. Discovery of the IRES
BOX 11.3. BACKGROUND. Use of the IRES in expression vectors
BOX 11.4. METHODS. Translation in vitro: the reticulocyte lysate and wheat germ extract
Elongation and Termination
The Diversity of Viral Translation Strategies
Polyprotein Synthesis
Leaky Scanning
BOX 11.5. EXPERIMENTS. Raiders of the lost ORF
Reinitiation
StopGo Translation
Suppression of Termination
Ribosomal Frameshifting
Bicistronic mRNAs
Regulation of Translation during Viral Infection
Inhibition of Translation Initiation after Viral Infection. Phosphorylation of eIF2α
Viral Regulation of PKR
Beneficial Effects of eIF2α Phosphorylation on Viral Reproduction
Regulation of eIF4F
Cleavage of eIF4G
Modulation of eIF4E Activity by Phosphorylation
Modulation of eIF4E Activity by Binding Proteins
Modulation of eIF4E by miRNA
A Viral Protein That Replaces eIF4F
A Viral Cap-Binding Protein
Regulation of Poly(A)-Binding Protein Activity
Regulation of eIF3
Interfering with RNA
Modification of Ribosomal Proteins
N6-Methyladenosine Modification of RNA
Stress-Associated RNA Granules
Perspectives
REFERENCES. Review Articles
Papers of Special Interest
STUDY QUESTIONS
12 Intracellular Trafficking
LINKS FOR CHAPTER 12
Introduction
PRINCIPLES Intracellular trafficking
BOX 12.1. DISCUSSION. Getting from point A to point B in heavy traffic
Assembly within the Nucleus
BOX 12.2. BACKGROUND. Cytoskeletal proteins also facilitate virus reproduction in bacteria
BOX 12.3. DISCUSSION. A separation of convenience: transport and assembly of components of virus particles
Import of Viral Proteins for Assembly
Assembly at the Plasma Membrane
BOX 12.4. DISCUSSION. Does host cell architecture shape virus structure?
Transport of Viral Membrane Proteins to the Plasma Membrane
Translocation of Viral Membrane Proteins into the Endoplasmic Reticulum
Reactions within the ER
BOX 12.5. EXPERIMENTS. Viruses with a sweet tooth: autonomous glycosylation of viral proteins
BOX 12.6. DISCUSSION. The evolving sugar “shield” of human immunodeficiency virus type 1
BOX 12.7. DISCUSSION. Overcoming the cellular compartmentalization of oxidation-reduction potential
Vesicular Transport to the Cell Surface
BOX 12.8. TRAILBLAZER. A viral glycoprotein exploited to identify the ER retrotranslocation machinery
BOX 12.9. EXPERIMENTS. Characterizing ER-to-Golgi transport using a temperature-sensitive viral protein
Sorting of Viral Proteins in Polarized Cells
Epithelial Cells
Neurons
Disruption of the Secretory Pathway in Virus-Infected Cells. Inhibition of Transport of Cellular Proteins
Drastic Effects on Compartments of the Secretory Pathway
Induction or Inhibition of the Unfolded Protein Response
Signal Sequence-Independent Transport of Viral Proteins to the Plasma Membrane
Lipid-plus-Protein Signals
Protein Sequence Signals
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. Reviews
Papers of Special Interest
STUDY QUESTIONS
13 Assembly, Release, and Maturation
LINKS FOR CHAPTER 13
Introduction
Methods of Studying Virus Assembly and Egress
PRINCIPLES Assembly, release, and maturation
Structural Studies of Virus Particles
Visualization of Assembly and Exit by Microscopy
Biochemical and Genetic Analyses of Assembly Intermediates
BOX 13.1. BACKGROUND. Late steps in T4 assembly
BOX 13.2. METHODS. Assembly of herpes simplex virus 1 nucleocapsids in a simplified system
Methods Based on Recombinant DNA Technology
Assembly of Protein Shells
Formation of Structural Units
Assembly from Individual Proteins
Assembly from Polyproteins
Participation of Cellular and Viral Chaperones
Capsid and Nucleocapsid Assembly
Intermediates in Assembly
BOX 13.3. DISCUSSION. A continuous-assembly mechanism for some large DNA viruses?
Self-Assembly and Assisted Assembly Reactions
Viral and Cellular Components That Regulate Self-Assembly
Viral Scaffolding Proteins: Chaperones for Assembly
Selective Packaging of the Viral Genome and Other Components of Virus Particles. Concerted or Sequential Assembly
BOX 13.4. EXPERIMENTS. Visualization of structural transitions during assembly of DNA viruses
Recognition and Packaging of the Nucleic Acid Genome
Nucleic Acid Packaging Signals
BOX 13.5. DISCUSSION. Sequential or concerted assembly of adenovirus particles?
BOX 13.6. DISCUSSION. Viral terminase motors: powerful nanomachines for pushing DNA into capsids
BOX 13.7. EXPERIMENTS. Dimerization-induced conformational change and encapsidation of the human immunodeficiency virus type 1 genome
Packaging of Segmented Genomes
BOX 13.8. BACKGROUND. Packaging a headful of viral DNA
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
ESCRT-Dependent Budding
ESCRT-Independent Budding
Nonstructural Proteins Can Facilitate Release
Assembly at Internal Membranes: the Problem of Exocytosis. Cytoplasmic Compartments of the Secretory Pathway
Envelopment by a Virus-Specific Mechanism
Intranuclear Assembly
BOX 13.9. EXPERIMENTS. Repulsion of virus particles from infected cells accelerates vaccinia virus spread
Release of Nonenveloped Virus Particles
Maturation of Progeny Virus Particles. Proteolytic Processing of Structural Proteins
BOX 13.10. BACKGROUND. A bacteriophage paradigm for lysis of host cells
Cleavage of Polyproteins
Cleavage of Precursor Proteins
Other Maturation Reactions
BOX 13.11. EXPERIMENTS. A notable example of virus maturation: extracellular assembly of specific structures
Cell-to-Cell Spread
BOX 13.12. BACKGROUND. Extracellular and cell-to-cell spread
BOX 13.13. DISCUSSION. Intercellular transport by plant virus movement proteins
Perspectives
REFERENCES. Reviews
Papers of Special Interest
STUDY QUESTIONS
14 The Infected Cell
LINKS FOR CHAPTER 14
Introduction
Signal Transduction. Signaling Pathways
PRINCIPLES The infected cell
BOX 14.1. TERMINOLOGY. How to interpret illustration of signal transduction cascades in this text
Signaling in Virus-Infected Cells
Activation of Common Signaling Pathways
Infection with a Particular Virus Modulates Multiple Signal Transduction Pathways
BOX 14.2. DISCUSSION. Outcomes of virus infection governed by AKT and mTOR signaling
Gene Expression
Inhibition of Cellular Gene Expression
BOX 14.3. DISCUSSION. A virus infection-induced feedback loop linking mRNA turnover to transcription
BOX 14.4. BACKGROUND. Multiple parameters govern the steady-state concentration of a cellular mRNA
Differential Regulation of Cellular Gene Expression
BOX 14.5. DISCUSSION. Insights into virus-host interactions from RNA profiling studies
BOX 14.6. DISCUSSION. Rewiring host cell networks: viral hub proteins
Metabolism
Methods To Study Metabolism
Glucose Metabolism
BOX 14.7. EXPERIMENTS. Members of the same virus family can exert different effects on metabolism: glycolysis in cells infected by two human herpesviruses
Virus Infection Can Alter the Rate of Glycolysis by Several Mechanisms
Virus Infection Can Redirect the Utilization of Glycolytic Intermediates and Products
BOX 14.8. EXPERIMENTS. Relocation of an ATP-generating enzyme to support viral genome replication
Human Disease Associated with Virus-Induced Alterations in Glucose Metabolism
The Citric Acid Cycle
Enhanced Replenishment of the Citric Acid Cycle by Metabolism of Glutamine
Electron Transport and Oxidative Phosphorylation
BOX 14.9. EXPERIMENTS. Vaccinia virus infection stimulates both synthesis and degradation of long-chain fatty acids
Lipid Metabolism
Regulation of Fatty Acid Oxidation in Virus-Infected Cells
Infection by Several Enveloped Viruses Stimulates Fatty Acid Synthesis
BOX 14.10. DISCUSSION. Dengue virus infection induces autophagy to mobilize fatty acids for energy generation
Reprogramming of Lipid Metabolism in Cells Infected by Nonenveloped Picornaviruses
Remodeling of Cellular Organelles
BOX 14.11. DISCUSSION. Does infection by human adenovirus type 36 contribute to obesity in humans?
The Nucleus
BOX 14.12. EXPERIMENTS. Counting the number of herpesviral genomes that can be expressed and replicated
The Cytoplasm
Cytoplasmic Viral Factories
BOX 14.13. EXPERIMENTS. Examining remodeling of organelles in virus-infected cells
Replication and Assembly Platforms
Other Cytoplasmic Organelles
Perspectives
REFERENCES. Review Articles
Papers of Special Interest
STUDY QUESTIONS
APPENDIX Structure, Genome Organization, and Infectious Cycles of Viruses Featured in This Book. Adenoviruses. Family Adenoviridae
Arenaviruses. Family Arenaviridae
Coronaviruses. Family Coronaviridae
Filoviruses. Family Filoviridae
Flaviviruses. Family Flaviviridae
Hepadnaviruses. Family Hepadnaviridae
Herpesviruses. Family Herpesviridae
Orthomyxoviruses. Family Orthomyxoviridae
Paramyxoviruses. Family Paramyxoviridae
Parvoviruses. Family Parvoviridae
Picornaviruses. Family Picornaviridae
Polyomaviruses. Family Polyomaviridae
Poxviruses. Family Poxviridae
Reoviruses. Family Reoviridae
Retroviruses. Family Retroviridae
Rhabdoviruses. Family Rhabdoviridae
Togaviruses. Family Togaviridae
Glossary
Index. A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
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