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Jane Flint
Principles of Virology
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Страница 1
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Страница 7
VOLUME I
Molecular Biology
PRINCIPLES OF
Virology
Страница 9
Страница 10
About the Instructor Companion Website
Страница 12
Acknowledgments
About the Authors
Key of Repetitive Elements
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
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
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