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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Serie: ASM
- Sprache: Englisch
Principles of Virology, the leading virology textbook in use, is an extremely valuable and highly informative presentation of virology at the interface of modern cell biology and immunology. This text utilizes a uniquely rational approach by highlighting common principles and processes across all viruses. Using a set of representative viruses to illustrate the breadth of viral complexity, students are able to under-stand viral reproduction and pathogenesis and are equipped with the necessary tools for future encounters with new or understudied viruses.
This fifth edition was updated to keep pace with the ever-changing field of virology. In addition to the beloved full-color illustrations, video interviews with leading scientists, movies, and links to exciting blogposts on relevant topics, this edition includes study questions and active learning puzzles in each chapter, as well as short descriptions regarding the key messages of references of special interest.
Volume I: Molecular Biology focuses on the molecular processes of viral reproduction, from entry through release. Volume II: Pathogenesis and Control addresses the interplay between viruses and their host organisms, on both the micro- and macroscale, including chapters on public health, the immune response, vaccines and other antiviral strategies, viral evolution, and a brand new chapter on the therapeutic uses of viruses. These two volumes can be used for separate courses or together in a single course. Each includes a unique appendix, glossary, and links to internet resources.
Principles of Virology, Fifth Edition, is ideal for teaching the strategies by which all viruses reproduce, spread within a host, and are maintained within populations. This edition carefully reflects the results of extensive vetting and feedback received from course instructors and students, making this renowned textbook even more appropriate for undergraduate and graduate courses in virology, microbiology, and infectious diseases.
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Seitenzahl: 1796
Veröffentlichungsjahr: 2020
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Table of Contents
Cover
Preface
What’s New
Principles Taught in Two Distinct, but Integrated Volumes
Acknowledgments
About the Authors
Key of Repetitive Elements
PART I: The Science of Virology
1 Foundations
Luria’s Credo
Viruses Defined
Why We Study Viruses
Virus Prehistory
Discovery of Viruses
The Defining Properties of Viruses
Cataloging Animal Viruses
A Common Strategy for Viral Propagation
Perspectives
References
2 The Infectious Cycle
Introduction
The Infectious Cycle
Viral Pathogenesis
Overcoming Host Defenses
Cultivation of Viruses
Assay of Viruses
Viral Reproduction: the Burst Concept
The One-Step Growth Cycle
Global Analysis
Single-Cell Virology
Perspectives
References
PART II: Molecular Biology
3 Genomes and Genetics
Introduction
Genome Principles and the Baltimore System
Structure and Complexity of Viral 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
Perspectives
References
4 Structure
Introduction
Building a Protective Coat
Packaging the Nucleic Acid Genome
Viruses with Envelopes
Large Viruses with Multiple Structural Elements
Other Components of Virions
Mechanical Properties of Virus Particles
Perspectives
References
5 Attachment and Entry
Introduction
Attachment of Virus Particles to Cells
Entry into Cells
Intracellular Trafficking and Uncoating
Import of Viral Genomes into the Nucleus
Perspectives
References
6 Synthesis of RNA from RNA Templates
Introduction
The Nature of the RNA Template
The RNA Synthesis Machinery
Mechanisms of RNA Synthesis
Paradigms for Viral RNA Synthesis
Origins of Diversity in RNA Virus Genomes
Perspectives
References
7 Synthesis of RNA from DNA Templates
Introduction
Transcription by RNA Polymerase II
Transcription of Viral DNA Templates by the Cellular Machinery Alone
Viral Proteins That Govern Transcription of DNA Templates
Transcription of Viral Genes by RNA Polymerase III
Inhibition of the Cellular Transcriptional Machinery
Unusual Functions of Cellular Transcription Components in Virus-Infected Cells
Viral DNA-Dependent RNA Polymerases
Perspectives
References
8 Processing
Introduction
Covalent Modification during Viral Pre-mRNA Processing
Export of RNAs from the Nucleus
Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins
Regulation of Turnover of Viral and Cellular mRNAs in the Cytoplasm
Noncoding RNAs
Perspectives
References
9 Replication of DNA Genomes
Introduction
DNA Synthesis by the Cellular Replication Machinery
Mechanisms of Viral DNA Synthesis
Exponential Accumulation of Viral Genomes
Limited Replication of Viral DNA Genomes
Origins of Genetic Diversity in DNA Viruses
Perspectives
References
10 Reverse Transcription and Integration
Retroviral Reverse Transcription
Retroviral DNA Integration
Hepadnaviral Reverse Transcription
Perspectives
References
11 Protein Synthesis
Introduction
Mechanisms of Eukaryotic Protein Synthesis
The Diversity of Viral Translation Strategies
Regulation of Translation during Viral Infection
Perspectives
References
12 Intracellular Trafficking
Introduction
Assembly within the Nucleus
Assembly at the Plasma Membrane
Interactions with Internal Cellular Membranes
Transport of Viral Genomes to Assembly Sites
Perspectives
References
13 Assembly, Release, and Maturation
Introduction
Methods of Studying Virus Assembly and Egress
Assembly of Protein Shells
Selective Packaging of the Viral Genome and Other Components of Virus Particles
Acquisition of an Envelope
Release of Virus Particles
Maturation of Progeny Virus Particles
Cell-to-Cell Spread
Perspectives
References
14 The Infected Cell
Introduction
Signal Transduction
Gene Expression
Metabolism
Remodeling of Cellular Organelles
Perspectives
References
APPENDIX: Structure, Genome Organization, and Infectious Cycles of Viruses Featured in This Book
Adenoviruses
Arenaviruses
Coronaviruses
Filoviruses
Flaviviruses
Hepadnaviruses
Herpesviruses
Orthomyxoviruses
Paramyxoviruses
Parvoviruses
Picornaviruses
Polyomaviruses
Poxviruses
Reoviruses
Retroviruses
Rhabdoviruses
Togaviruses
Glossary
Index
End User License Agreement
List of Tables
Chapter 2
Table 2.1 Particle-to-PFU ratios of some animal viruses
Chapter 3
Table 3.1 Some viral vectors
Chapter 4
Table 4.1 Functions of virion proteins
Table 4.2 Nomenclature used in description of virus structure
Table 4.3 Some virion enzymes
Chapter 7
Table 7.1 Strategies of transcription of viral DNA templates
Table 7.2 Eukaryotic RNA polymerases synthesize different classes of cellular an...
Table 7.3 Properties and functions of some viral transcriptional regulators
Table 7.4 Viral RNA polymerase III transcription units
Chapter 9
Table 9.1 Viral origin recognition proteins
Table 9.2 Replication systems of large DNA viruses
Table 9.3 Viral enzymes of nucleic acid metabolism
Chapter 10
Table 10.1 Comparison of retroviral integration site preferences in human cells
Table 10.2 Comparison of retroviral and hepadnaviral reverse transcription
Chapter 12
Table 12.1 Some viral envelope glycoprotein precursors processed by secretory pa...
Chapter 13
Table 13.1 Common sequence motifs required for budding of enveloped virus partic...
List of Illustrations
Chapter 1
Figure 1.1 The human virome. Our knowledge of the diversity of viruses that ca...
Figure 1.2 Tracking ancient human migrations by the viruses they carried. The ...
Figure 1.3 References to viral diseases from the ancient literature.
(A)
An im...
Figure 1.4 Three Broken Tulips . A painting by Nicolas Robert (1624–1685), now ...
Figure 1.5 Characteristic smallpox lesions in a young victim. Illustrations li...
Figure 1.6 Pasteur’s famous swan-neck flasks provided passive exclusion of micro...
Figure 1.7 The pace of discovery of new infectious agents in the dawn of virolog...
Figure 1.8 Filter systems used to characterize/purify virus particles.
(A)
The...
Figure 1.9 Electron micrographs of virus particles following negative staining. ...
Figure 1.10 Size matters.
(A)
Sizes of animal and plant cells, bacteria, virus...
Figure 1.11 Lesions induced by tobacco mosaic virus on an infected tobacco leaf....
Figure 1.12 The Baltimore classification. The Baltimore classification assigns...
Figure 1.13 Viral families sorted according to the nature of the viral genomes. ...
Figure 1.14 Landmarks in the study of viruses. Key discoveries and technical a...
Chapter 2
Figure 2.1 The viral infectious cycle. The infectious cycle of poliovirus is s...
Figure 2.2 Different types of cell culture used in virology. Confluent cell mo...
Figure 2.3 Production of organoids from stem cells. The different germ layers ...
Figure 2.4 Production of airway-liquid interface cultures of bronchial epithel...
Figure 2.5 Development of cytopathic effect.
(A)
Cell rounding and lysis durin...
Figure 2.6 Growth of viruses in embryonated eggs. The cutaway view of an embry...
Figure 2.7 Plaques formed by different animal viruses.
(A)
Photomicrograph of ...
Figure 2.8 The dose-response curve of the plaque assay. The number of plaques ...
Figure 2.9 Transformation assay. Chicken cells transformed by two different st...
Figure 2.10 Hemagglutination assay. (
Top
) Samples of different influenza virus...
Figure 2.11 Polysome analysis. To study the association of mRNAs with ribosome...
Figure 2.12 Direct and indirect methods for antigen detection.
(A)
The sample ...
Figure 2.13 Detection of viral antigen or antibodies against viruses by enzyme...
Figure 2.14 Lateral flow immunochromatographic assay. A slide or “dipstick” co...
Figure 2.15 Using fluorescent proteins to study virus particles and virus-infe...
Figure 2.16 Polymerase chain reaction. The DNA to be amplified is mixed with n...
Figure 2.17 Workflow for VS-Virome. Shown is the computational pipeline design...
Figure 2.18 Comparison of bacterial and viral reproduction.
(A)
Growth curve f...
Figure 2.19 One-step growth curves of animal viruses.
(A)
Growth of a nonenvel...
Figure 2.20 Chromatin immunoprecipitation and DNA sequencing, ChiP-seq. This t...
Figure 2.21 Interactions between human proteins and Nipah virus proteins. Netw...
Figure 2.22 Single-cell virology.
(A)
A microfluidic device with 6,400 wells i...
Chapter 3
Figure 3.1 The Baltimore classification. All viruses must produce mRNA that ca...
Figure 3.2 Structure and expression of viral double-stranded DNA genomes.
(A)
...
Figure 3.3 Structure and expression of viral gapped, circular, double-stranded D...
Figure 3.4 Structure and expression of viral single-stranded DNA genomes.
(A)
...
Figure 3.5 Structure and expression of viral double-stranded RNA genomes.
(A)
...
Figure 3.6 Structure and expression of viral single-stranded (+) RNA genomes.
Figure 3.7 Structure and expression of viral single-stranded (+) RNA genomes wit...
Figure 3.8 Structure and expression of viral single-stranded (–) RNA genomes.
Figure 3.9 Genome structures in cartoons and in real life.
(A)
Linear represen...
Figure 3.10 Information retrieval from viral genomes. Different strategies for...
Figure 3.11 Reassortment of influenza virus RNA segments.
(A)
Progeny viruses ...
Figure 3.12 Recovery of infectivity from cloned DNA of RNA viruses.
(A)
The in...
Figure 3.13 Use of RNAi, haploid cells, and CRISPR-Cas9 to study virus-host inte...
Figure 3.14 Adenovirus vectors. High-capacity adenovirus “gutless” vectors con...
Figure 3.15 Adeno-associated virus vectors.
(A)
Map of the genome of wild-type...
Figure 3.16 Retroviral vectors. The minimal viral sequences required for retro...
Chapter 4
Figure 4.1 Variation in the size and shape of virus particles.
(A)
Cryo-electr...
Figure 4.2 Free energy changes in virus particles. Mature virus particles occu...
Figure 4.3 Cryo-EM and image reconstruction illustrated with rotavirus.
Figure 4.4 Determination of virus structure by X-ray diffraction. This method ...
Figure 4.5 Difference mapping illustrated by a 6-Å-resolution reconstruction of ...
Figure 4.6 Virus structures with helical symmetry.
(A)
Schematic illustration ...
Figure 4.7 Structure of a ribonucleoprotein-like complex of vesicular stomatitis...
Figure 4.8 Structure of an influenza A virus ribonucleoprotein.
(A)
(Left) Rib...
Figure 4.9 Icosahedral packing in simple structures.
(A)
An icosahedron, which...
Figure 4.10 The principle of triangulation: formation of large capsids with icos...
Figure 4.11 Structure of the parvovirus adeno-associated virus 2.
(A)
Ribbon d...
Figure 4.12 Packing and structures of poliovirus proteins.
(A)
The packing of ...
Figure 4.13 Interactions among the proteins of the poliovirus capsid.
(A)
Ribb...
Figure 4.14 Structural features of simian virus 40.
(A)
View of the simian vir...
Figure 4.15 Structural features of adenovirus particles.
(A)
The organization ...
Figure 4.16 Interactions among major and minor proteins of the adenoviral capsid...
Figure 4.17 Structures of members of the Reoviridae. The organization of mamma...
Figure 4.18 Asymmetric capsids of retroviruses.
(A)
Variation in the morpholog...
Figure 4.19 Ordered RNA genomes in small and large icosahedral virus particles. ...
Figure 4.20 Packing of double-stranded DNA genome.
(A)
Dense packing in the he...
Figure 4.21 Conserved organization of the RNA-packaging proteins of nonsegmented...
Figure 4.22 Structural and chemical features of a typical viral envelope glycopr...
Figure 4.23 Structures of extracellular domains of viral glycoproteins. These ...
Figure 4.24 Structure of a simple enveloped virus, Sindbis virus.
(A)
Cross se...
Figure 4.25 Conserved topology and regular packing of envelope proteins of small...
Figure 4.26 Morphological complexity of bacteriophage T4.
(A)
A model of the v...
Figure 4.27 Structural features of herpesvirus particles.
(A)
Two slices throu...
Figure 4.28 Features of mimivirus capsids.
(A)
Cryo-EM reconstruction of
Cafet
...
Figure 4.29 Virus particles with alternative architectures. Structural feature...
Figure 4.30 Atomic force microscopy and its application to human adenovirus part...
Chapter 5
Figure 5.1 Architecture of cell surfaces. Example of epithelial cells with api...
Figure 5.2 Experimental strategies for identification and isolation of genes enc...
Figure 5.3 Some receptors for virus particles. Schematic diagrams of cell mole...
Figure 5.4 Picornavirus-receptor interactions.
(A)
Structure of poliovirus bou...
Figure 5.5 Structure of the adenovirus 12 knob bound to the CAR receptor.
(A)
...
Figure 5.6 Entry of polyomavirus simian virus 40. Simian virus 40 interacts fi...
Figure 5.7 Interaction of sialic acid receptors with the hemagglutinin of influe...
Figure 5.8 Interaction of human immunodeficiency virus type 1 envelope glycoprot...
Figure 5.9 Multiple receptors for herpes simplex virus 1 (HSV-1). Six (of 15) ...
Figure 5.10 Mechanisms for the uptake of macromolecules from extracellular fluid...
Figure 5.11 Virus entry and movement in the cytoplasm. Examples of various rou...
Figure 5.12 Conformational changes of class I proteins during fusion. The enve...
Figure 5.13 Influenza virus entry. The globular heads of HA trimers mediate bi...
Figure 5.14 Conservation of the hairpin structure in class I viral fusion protei...
Figure 5.15 Fusion at the plasma membrane. (Top) Model for human immunodeficie...
Figure 5.16 Entry of Ebolavirus into cells. Virus particles bind cells via an ...
Figure 5.17 SNARE-mediated fusion. The change of syntaxin (t-SNARE, purple) fr...
Figure 5.18 Conformational changes in class II proteins during fusion.
(A)
Nin...
Figure 5.19 Conformational changes in class III proteins during fusion. Struct...
Figure 5.20 Entry of Semliki Forest virus into cells. Semliki Forest virus ent...
Figure 5.21 Stepwise uncoating of adenovirus.
(A)
Adenovirus fiber proteins bi...
Figure 5.22 Model for poliovirus entry into cells. The native virus particle (...
Figure 5.23 Entry of reovirus into cells.
(A)
The different stages in cell ent...
Figure 5.24 Structure and organization of the nuclear pore complex. (Bottom le...
Figure 5.25 Nuclear localization signals. The general form and specific exampl...
Figure 5.26 Different strategies for entering the nucleus.
(A)
Each segment of...
Figure 5.27 Uncoating of adenovirus at the nuclear pore complex. After release...
Chapter 6
Figure 6.1 Strategies for replication and mRNA synthesis of RNA virus genomes ar...
Figure 6.2 RNA secondary structure.
(A)
Schematic of different structural moti...
Figure 6.3 Structure of viral ribonucleoproteins.
(A)
Space-filling model of v...
Figure 6.4 Protein domain alignments for the four categories of nucleic acid pol...
Figure 6.5 Structural elements of viral RNA-dependent RNA polymerase.
(A)
Ribb...
Figure 6.6 Structure of UTP bound to poliovirus 3Dpol. The NTP bridges the fin...
Figure 6.7 Mechanisms of initiation of RNA synthesis.
De novo
initiation may o...
Figure 6.8 Mechanism of de novo initiation.
(A)
Ribbon diagram of RdRP of hepa...
Figure 6.9 Uridylylation of VPg.
(A)
Linkage of VPg to polioviral genomic RNA....
Figure 6.10 Poliovirus (−) strand RNA synthesis. The precursor of VPg, 3AB, co...
Figure 6.11 Influenza virus RNA synthesis.
(A)
Viral (−) strand genomes are te...
Figure 6.12 Activation of the influenza virus RNA polymerase by specific virion ...
Figure 6.13 Functional N- and C-terminal extensions of RNA polymerases. The sm...
Figure 6.14 Oligomerization of RNA-dependent RNA polymerases. Ribbon diagrams ...
Figure 6.15 Structure of a viral RNA helicase. The RNA helicase of the flavivi...
Figure 6.16 Genome structure and expression of an alphavirus, Sindbis virus. T...
Figure 6.17 Three RNA polymerases with distinct specificities in alphavirus-infe...
Figure 6.18 Nidoviral genome organization and expression.
(A)
Organization of ...
Figure 6.19 Vesicular stomatitis viral RNA synthesis. Viral (−) strand genomes...
Figure 6.20 Stop-start model of vesicular stomatitis virus mRNA synthesis. The...
Figure 6.21 Poly(A) addition and termination at an intergenic region during vesi...
Figure 6.22 Moving-template model for influenza virus mRNA synthesis. During R...
Figure 6.23 Arenavirus RNA synthesis. Arenaviruses contain two genomic RNA seg...
Figure 6.24 mRNA synthesis and replication of double-stranded RNA genomes. The...
Figure 6.25 Hepatitis delta virus RNA synthesis.
(A)
Schematic of the forms of...
Figure 6.26 Ribosome-RNA polymerase collisions. A strand of viral RNA is shown...
Figure 6.27 RNA recombination. Schematic representation of RNA recombination o...
Chapter 7
Figure 7.1 Conversion of viral genomes to templates for transcription by cellula...
Figure 7.2 RNA polymerase II transcriptional control elements. The site of ini...
Figure 7.3 Initiation of transcription by RNA polymerase II. Assembly of the c...
Figure 7.4 Variations in core RNA polymerase II promoter architecture. Variati...
Figure 7.5 Local regulatory sequences of three viral transcriptional control reg...
Figure 7.6 Organization of the archetypal simian virus 40 enhancer. The positi...
Figure 7.7 Modular organization of sequence-specific transcriptional activators....
Figure 7.8 Widespread cellular transcriptional activators of an avian retrovirus...
Figure 7.9 Mechanisms of stimulation of transcription by viral proteins. Cellu...
Figure 7.10 Cell-type-specific regulators bind to the transcriptional control re...
Figure 7.11 The cellular regulator NF-κB and its participation in viral transcri...
Figure 7.12 Human immunodeficiency type-1 TAR and the Tat protein.
(A)
The reg...
Figure 7.13 Stimulation of transcription elongation by the human immunodeficienc...
Figure 7.14 Molecular mechanisms of stimulation of human immunodeficiency virus ...
Figure 7.15 Common features of the simian virus 40 (SV40), human adenovirus type...
Figure 7.16 Organization and regulation of the Epstein-Barr virus Zta gene promo...
Figure 7.17 Models for transcriptional activation by the herpes simplex virus ty...
Figure 7.18 Conformational changes and recruitment of VP16 to herpes simplex vir...
Figure 7.19 The adenoviral E1A proteins bind to multiple transcriptional regulat...
Figure 7.20 Indirect stimulation of transcription by adenoviral E1A proteins.
Figure 7.21 Cellular repressors regulate the activity of the simian virus 40 lat...
Figure 7.22 The latency-associated transcripts of herpes simplex virus type 1. ...
Figure 7.23 Organization of viral RNA polymerase III promoters.
(A)
The human ...
Figure 7.24 Assembly of an initiation complex on a vaccinia virus early promoter...
Chapter 8
Figure 8.1 Processing of a viral or cellular pre-mRNA synthesized by RNA polymer...
Figure 8.2 The 5′ cap structure and its synthesis by cellular or viral enzymes. ...
Figure 8.3 A viral unimolecular assembly line for capping. The structure of th...
Figure 8.4 Cleavage and polyadenylation of vertebrate pre-mRNAs. The 3′ end of...
Figure 8.5 The vaccinia virus capping enzyme and 2′-O-methyltransferase process ...
Figure 8.6 Reversible N6 methylation of internal adenosine nucleosides. Intern...
Figure 8.7 Inhibition of assembly and release of virus particles by N6 A methyla...
Figure 8.8 Splicing of pre-mRNA. (A) Consensus splicing signals in cellular an...
Figure 8.9 The conserved mechanism of eukaryotic pre-mRNA splicing. (A) Pathwa...
Figure 8.10 Constitutive and alternative splicing. (A) In constitutive splicin...
Figure 8.11 Alternative polyadenylation and splicing control the production of b...
Figure 8.12 Control of RNA-processing reactions during retroviral gene expressio...
Figure 8.13 Alternative polyadenylation and splicing of adenoviral major late tr...
Figure 8.14 Cotranscriptional editing of measles virus mRNAs. (A) Proposed mec...
Figure 8.15 Editing of hepatitis delta virus RNA by double-stranded RNA adenosin...
Figure 8.16 Regulation of export of human immunodeficiency virus type 1 mRNAs by...
Figure 8.17 Features and mechanism of Rev protein-dependent export. (A) The fu...
Figure 8.18 Export of unspliced RNA of retroviruses with simple genomes and cell...
Figure 8.19 Regulation of alternative splicing of viral pre-mRNA. (A) The poly...
Figure 8.20 Inhibition of cellular pre-mRNA processing by viral proteins. The ...
Figure 8.21 Mechanisms of intrinsic cellular and viral mRNA decay. A major pat...
Figure 8.22 Viral proteins initiate mRNA degradation by different mechanisms. ...
Figure 8.23 Major pathways of nonsense-mediated mRNA degradation. Nonsense-med...
Figure 8.24 Synthesis and function of miRNAs. The precursors of miRNAs (pri-mi...
Figure 8.25 The miRNAs of simian virus 40. The circular simian virus 40 genome...
Figure 8.26 Cellular lncRNAs that facilitate or impair virus reproduction. Cel...
Chapter 9
Figure 9.1 Viral and cellular proteins that synthesize viral DNA genomes. The ...
Figure 9.2 Properties of replicons. (A) Electron micrographs of replicating si...
Figure 9.3 Semidiscontinuous DNA synthesis from a bidirectional origin. Synthe...
Figure 9.4 The 5′-end problem in replication of linear DNAs. (A) Incomplete sy...
Figure 9.5 The origin of simian virus 40 DNA replication. The positions in the...
Figure 9.6 Model of the recognition and unwinding of the simian virus 40 origin....
Figure 9.7 Synthesis of leading and lagging strands. The DNA polymerase (POL) ...
Figure 9.8 A model of the simian virus 40 replication machine. A replication m...
Figure 9.9 Function of topoisomerases during simian virus 40 DNA replication. ...
Figure 9.10 Replication of parvoviral DNA. (A) Sequence and secondary structur...
Figure 9.11 Replication of adenoviral DNA. Assembly of the viral preterminal p...
Figure 9.12 Features of the herpes simplex virus type 1 genome. The long (L) a...
Figure 9.13 Common features of viral origins of DNA replication. The simian vi...
Figure 9.14 Functional organization of simian virus 40 LT. The domains of LT a...
Figure 9.15 Structural homology among DNA-binding domains of viral origin recogn...
Figure 9.16 Model of origin loading of the papillomaviral E1 initiation protein ...
Figure 9.17 Crystal structure of the adenoviral single-stranded-DNA-binding prot...
Figure 9.18 Regulation of production of cellular and viral replication proteins....
Figure 9.19 Discrete sites of viral replication.
(A)
Cytoplasmic vaccinia viru...
Figure 9.20 Reorganization of PML bodies by the adenoviral E4 Orf3 protein. Mo...
Figure 9.21 Common features of the adenovirus-associated virus type 2 lTR and th...
Figure 9.22 Licensing of replication from Epstein-Barr virus OriP.
(A)
Organiz...
Figure 9.23 Regulation of papillomaviral DNA replication in epithelial cells. ...
Figure 9.24 Proofreading during synthesis. If permanently fixed into the genom...
Figure 9.25 The DNA damage response. Damage to the DNA genome, such as a doubl...
Figure 9.26 Association of cellular DNA damage response proteins with herpesvira...
Figure 9.27 General model for initiation of recombination-dependent replication....
Figure 9.28 Isomers of the herpes simplex virus type 1 genome. The organizatio...
Chapter 10
Figure 10.1 Human immunodeficiency type 1 capsid hexamers showing open and close...
Figure 10.2 The diploid retroviral genome and a dimerization domain. (A) The d...
Figure 10.3 Primer tRNA binding to a retroviral RNA genome. (Top) Linear repre...
Figure 10.4 Retroviral reverse transcription: initiation of (–) strand DNA synth...
Figure 10.5 Retroviral reverse transcription: first template exchange, mediated ...
Figure 10.6 Retroviral reverse transcription: (+) strand DNA synthesis primed fr...
Figure 10.7 Retroviral reverse transcription: the second template exchange and f...
Figure 10.8 Two models for recombination during reverse transcription. Virtual...
Figure 10.9 Domain and subunit relationships of the RTs of different retroviruse...
Figure 10.10 Ribbon representation of HIV-1 RT bound to a model RNA template-DNA...
Figure 10.11 Model for a DNA-RNA hybrid bound to HIV-1 RT. The RNA template-DN...
Figure 10.12 Evolutionary relatedness of RT-like enzymes in bacteria, archaea, e...
Figure 10.13 Retroelements resident in eukaryotic genomes and their representati...
Figure 10.14 Comparison of the structures of two RTs. (A) The DNA polymerase d...
Figure 10.15 Characteristic features of retroviral integration. Unintegrated l...
Figure 10.16 Three steps in the retroviral DNA integration process. Endonucleo...
Figure 10.17 Sequence preferences of integration sites. The figure shows the 5...
Figure 10.18 Models for chromatin tethering of retroviral preintegration complex...
Figure 10.19 Host proteins affect the integration process. The abundant host b...
Figure 10.20 Domain maps of integrase proteins from different retroviral genera,...
Figure 10.21 Crystal structure of the prototype foamy virus integrase tetramer b...
Figure 10.22 Arrangement of HIV-1 IN dimer interfaces in the absence of DNA and ...
Figure 10.23 Hepadnaviral DNA. The DNA in extracellular hepadnavirus particles...
Figure 10.24 Single-cell reproduction cycle for hepadnaviruses. Pathway 1 prov...
Figure 10.25 Essential
cis
-acting signals in pregenomic mRNA. The viral pregen...
Figure 10.26 Comparison of hepadnaviral and retroviral RTs. Linear maps of the...
Figure 10.27 Model for the assembly of hepadnavirus nucleocapsids. P protein i...
Figure 10.28 Critical steps in the pathway of hepadnavirus reverse transcription...
Figure 10.29 Model for (+) strand priming. Formation of a hairpin in the (–) s...
Figure 10.30 Comparison of the genome replication cycles of cauliflower mosaic v...
Chapter 11
Figure 11.1 Structure of eukaryotic and bacterial/archaeal mRNAs. UTR, untrans...
Figure 11.2 Ribosomes and tRNAs. (A) Model of a eukaryotic ribosome. The 80S r...
Figure 11.3 5′-cap-dependent assembly of the initiation complex. Initiation pr...
Figure 11.4 5′ -end-dependent initiation. (A) Schematic of eIF4G protein. Data...
Figure 11.5 Two mechanisms of methionine-independent initiation. (A) A sequenc...
Figure 11.6 Hypothetical model of ribosome shunting. The 40S ribosomal subunit...
Figure 11.7 Six types of IRES. The 5′ untranslated regions from genome RNAs of...
Figure 11.8 5′-end-independent initiation. (Top) Initiation on the type 1 or 2...
Figure 11.9 Long-range RNA-RNA interactions aid translation. (A) Activity of t...
Figure 11.10 Translation elongation. There are three tRNA-binding sites on the...
Figure 11.11 Translation termination. (A) Overview of termination. When a term...
Figure 11.12 Ribosome recycling. After peptide release, ABCE1 binds to eRF1 on...
Figure 11.13 Juxtaposition of mRNA ends. Shown is a juxtaposition of mRNA ends...
Figure 11.14 The diversity of viral translation strategies.
Figure 11.15 Polyprotein processing of picornaviruses and flaviviruses. (A) Pr...
Figure 11.16 Leaky scanning in the Sendai virus P/C gene. P and C protein open...
Figure 11.17 Reinitiation of translation. (A) (Top) Some mRNAs contain one or ...
Figure 11.18 Proposed mechanism of StopGo translation. A model for the site-sp...
Figure 11.19 Suppression of termination codons of retroviruses and alphaviruses....
Figure 11.20 Frameshifting on a retroviral mRNA. The structure of open reading...
Figure 11.21 Tandem model for –1 frameshifting. Slippage of the two tRNAs occu...
Figure 11.22 Schematic structures of three eIF2α kinases. Y-kinase, pseudokina...
Figure 11.23 Model of activation of PKR. PKR is maintained as an inactive mono...
Figure 11.24 Effect of eIF2α phosphorylation on catalytic recycling. eIF2-GTP ...
Figure 11.25 Some viral proteins and RNAs that counter inactivation of eIF2. V...
Figure 11.26 Inhibition of cellular translation in poliovirus-infected HeLa cell...
Figure 11.27 Regulation of eIF4F activity. eIF4F is composed of eIF4E, eIF4G, ...
Figure 11.28 The mammalian PI3K-AKT-mTOR signaling route. The core features of...
Figure 11.29 Stress granule assembly and inhibition by viral proteins. When pr...
Chapter 12
Figure 12.1 Localization of viral proteins to the nucleus. The nucleus and maj...
Figure 12.2 Localization of viral proteins to the plasma membrane. Viral envel...
Figure 12.3 Primary sequence features and covalent modifications of the influenz...
Figure 12.4 Maturation of influenza virus HA0 protein during transit along the s...
Figure 12.5 The endoplasmic reticulum. (A) The ER of a mammalian cell in cultu...
Figure 12.6 Canonical targeting of a nascent protein to the ER membrane. Trans...
Figure 12.7 Detection and synthesis of N-linked oligosaccharides. (A) Detectio...
Figure 12.8 Integration of folding and glycosylation in the ER. (A) The model ...
Figure 12.9 Folding of the two Sindbis virus envelope proteins depends on format...
Figure 12.10 Compartments in the secretory pathway. Proteins destined for secr...
Figure 12.11 Protein transport from the ER to the Golgi apparatus. (A) Protein...
Figure 12.12 Low-pH-induced conformational change and maturation of dengue virus...
Figure 12.13 Polarized epithelial cells and neurons. (A) Tight junctions block...
Figure 12.14 Axonal transport of herpesviral particles in neurons. (A) At the ...
Figure 12.15 Modulation of the unfolded protein response in virus-infected cells...
Figure 12.16 Addition of lipids to cytoplasmic proteins. (A) N-terminal myrist...
Figure 12.17 Targeting signals of human immunodeficiency virus type 1 Gag protei...
Figure 12.18 Targeting signals of matrix proteins of influenza virus (A) and ves...
Figure 12.19 Sorting of viral glycoproteins to internal cell membranes. The de...
Figure 12.20 Transport of influenza A virus genomic RNA segments from the nucleu...
Figure 12.21 Models of the rhabdovirus nucleocapsid, showing the free nucleocaps...
Figure 12.22 Cytoplasmic trafficking of retroviral genomes with different nuclea...
Chapter 13
Figure 13.1 Pathways of virus particle assembly and release. The structural un...
Figure 13.2 Examination of virus assembly by high-resolution microscopy. Incre...
Figure 13.3 Mechanisms of assembly of viral structural units. (A) Assembly fro...
Figure 13.4 Radial organization of the Gag polyprotein in immature human immunod...
Figure 13.5 Some assembly reactions assisted by cellular chaperones. (A) The
E
...
Figure 13.6 Assembly of poliovirus in the cytoplasm of an infected cell. (A) M...
Figure 13.7 Formation of bullet-shaped particles by the vesicular stomatitis vir...
Figure 13.8 Assembly of herpes simplex virus 1 nucleocapsids. (A) Assembly beg...
Figure 13.9 Assembly of influenza A virus. Assembly proceeds in stepwise fashi...
Figure 13.10 Assembly of a retrovirus from polyprotein precursors. The Gag pol...
Figure 13.11 Viral DNA-packaging signals. (A) Human adenovirus type 5 (Ad5). T...
Figure 13.12 Packaging of herpes simplex virus 1 DNA. (A) Organization of the ...
Figure 13.13 Sequences important for the packaging of retroviral genomes. (A) ...
Figure 13.14 Organization of ribonucleoproteins in influenza A virus particles. ...
Figure 13.15 Interaction of viral proteins responsible for budding at the plasma...
Figure 13.16 L domains and release of retroviral particles. (A) Electron micro...
Figure 13.17 Functions of the ESCRT pathway in uninfected and virus-infected cel...
Figure 13.18 Model of hepatitis B virus envelopment. The pregenome RNA synthes...
Figure 13.19 Vaccinia virus assembly and exocytosis. Viral structures observed...
Figure 13.20 Movement of vaccinia virus on actin tails. (A) Immunofluorescence...
Figure 13.21 Pathway of herpesvirus egress. The mature nucleocapsid assembled ...
Figure 13.22 Disruption of the nuclear lamina in herpes simplex virus 1-infected...
Figure 13.23 Models for nonlytic release of picornavirus particles. (A) Synthe...
Figure 13.24 Morphological rearrangement of retrovirus particles upon proteolyti...
Figure 13.25 Model for refolding of the human immunodeficiency virus type 1 CA p...
Figure 13.26: The maturation of hepatitis B virus particles. (A) Alternative t...
Figure 13.27 Direct cell-to-cell spread of virus particles. (A) Human immunode...
Chapter 14
Figure 14.1 The mammalian PI3K-AKT-mTOR signaling route. The core features of ...
Figure 14.2 Signaling via PI3K facilitates virus entry. Shown are three exampl...
Figure 14.3 Common activation of the PI3K-AKT-mTOR relay in virus-infected cells...
Figure 14.4 Inhibition of cellular gene expression by viral proteins. (Transcr...
Figure 14.5 Decreases in cellular mRNA concentration in virus-infected cells. ...
Figure 14.6 Polyribosome profiling. Shown is a comparison of the polyribosome ...
Figure 14.7 Reprogramming of promoter-associated transcriptional regulators by a...
Figure 14.8 Increased glycolysis in virus-infected cells. (A) Infection by a v...
Figure 14.9 Glucose metabolism. Following transport into cells via glucose tra...
Figure 14.10 Diversion of acetyl-CoA for fatty acid synthesis in human cytomegal...
Figure 14.11 The citric acid cycle and some alterations induced in virus-infecte...
Figure 14.12 The electron transport chain and oxidative phosphorylation. The e...
Figure 14.13 Storage and mobilization of fatty acids. (A) Fatty acids are tran...
Figure 14.14 Mechanisms of stimulation of fatty acid synthesis in human cytomega...
Figure 14.15 Increased synthesis and accumulation of fatty acids in hepatitis C ...
Figure 14.16 Increased import of fatty acids into poliovirus-infected cells. (...
Figure 14.17 Reorganization of nuclei in polyomavirus-infected cells. Murine 3...
Figure 14.18 Example of a PML-containing nuclear structure in DNA virus-infected...
Figure 14.19 Reorganization of nuclear splicing components in DNA virus-infected...
Figure 14.20 Dengue virus cytoplasmic replication and assembly organelles. Hum...
Figure 14.21 Hepatitis C virus replication and assembly compartments. (A) The ...
Figure 14.22 Cooption of cytoplasmic membranes and lipid droplets in poliovirus-...
Figure 14.23 Initial rotavirus assembly on lipid droplets. (A) The kinetics of...
Appendix
Figure 1 Structure and genome organization of human adenovirus type 5.
(A) Vir
...
Figure 2 Infectious cycle of human adenovirus type 5.
(1)
The virus attaches t...
Figure 3 Structure and genome organization.
(A) Virus particle structure.
Cryo...
Figure 4 Infectious cycle.
(1, 2)
The virion binds to a cellular receptor, whi...
Figure 5 Structure and genome organization of murine coronavirus.
(A) Virus pa
...
Figure 6 Infectious cycle.
(1)
The virus particle binds to a cell surface rece...
Figure 7 Structure and genome organization of the filovirus Zaire ebolavirus.
Figure 8 Infectious cycle of ebolavirus.
(1)
Virus particles bind to a cell su...
Figure 9 Structure and genome organization of flaviviruses.
(A) Virus particle
...
Figure 10 Infectious cycle.
(1)
The virus particle binds to a cell surface rec...
Figure 11 Structure and genome organization of orthohepadnaviruses.
(A) Virus
...
Figure 12 Infectious cycle of hepatitis B virus.
(1)
The virion attaches to a ...
Figure 13 Structure and genome organization of alphaherpesviruses.
(A) Virus p
...
Figure 14 Infectious cycle of herpes simplex virus type 1.
(1)
Virions bind to...
Figure 15 Structure and genome organization of the orthomyxovirus influenza A vi...
Figure 16 Infectious cycle of influenza A virus.
(1)
The virion binds to a sia...
Figure 17 Structure and genome organization.
(A) Virus particle structure.
Ima...
Figure 18 Infectious cycle.
(1)
The virion attaches by binding to specific rec...
Figure 19 Structure and genome organization of adenovirusassociated virus (AAV)...
Figure 20 Infectious cycle of adenovirusassociated virus (AAV). Heparan sulfa...
Figure 21 Structure and genomic organization of poliovirus.
(A) Virus particle
...
Figure 22 Infectious cycle of poliovirus.
(1)
The virion binds to a cellular r...
Figure 23 Structure and genome organization of simian virus 40.
(A) Virus part
...
Figure 24 Infectious cycle of simian virus 40.
(1)
The virus particle attaches...
Figure 25 Structure and genome organization of the poxvirus vaccinia virus.
(A
...
Figure 26 Infectious cycle of vaccinia virus.
(1)
After receptor binding and f...
Figure 27 Structure and genomic organization of an orthoreovirus.
(A) Virus pa
...
Figure 28 Infectious cycle of orthoreovirus.
(1)
The virion binds to cellular ...
Figure 29 Structure and genomic organization.
(A) Virus particle structure.
Th...
Figure 30 Infectious cycle of a retrovirus with a simple genome.
(1)
The virus...
Figure 31 Structure and genomic organization of vesicular stomatitis virus.
(A
...
Figure 32 Infectious cycle.
(1)
The virion binds to a cellular receptor, such ...
Figure 33 Structure and genomic organization.
(A) Virus particle structure.
Th...
Figure 34 Infectious cycle.
(1)
The virion binds to a cellular receptor and en...
Guide
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VOLUME I Molecular Biology
PRINCIPLES OFVirology
FIFTH EDITION
Jane Flint
Department of Molecular BiologyPrinceton UniversityPrinceton, New Jersey
Vincent R. Racaniello
Department of Microbiology & ImmunologyVagelos College of Physicians and SurgeonsColumbia UniversityNew York, New York
Glenn F. Rall
Fox Chase Cancer CenterPhiladelphia, Pennsylvania
Theodora Hatziioannou
The Rockefeller UniversityNew York, New York
Anna Marie Skalka
Fox Chase Cancer CenterPhiladelphia, Pennsylvania
Copyright © 2020 American Society for Microbiology. All rights reserved.
Copublication by the American Society for Microbiology and John Wiley & Sons, Inc.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted by law. Advice on how to reuse material from this title is available at http://wiley.com/go/permissions.
The right of Jane Flint, Vincent R. Racaniello, Glenn F. Rall, Theodora Hatziioannou, and Anna Marie Skalka to be identified as the author(s) of this work/the editorial material in this work has been asserted in accordance with law.
Limit of Liability/Disclaimer of Warranty
While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy of completeness of the contents of this book and specifically disclaim any implied warranties or merchantability of fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The publisher is not providing legal, medical, or other professional services. Any reference herein to any specific commercial products, procedures, or services by trade name, trademark, manufacturer, or otherwise does not constitute or imply endorsement, recommendation, or favored status by the American Society for Microbiology (ASM). The views and opinions of the author(s) expressed in this publication do not necessarily state or reflect those of ASM, and they shall not be used to advertise or endorse any product.
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Library of Congress Cataloging-in-Publication Data
Names: Flint, S. Jane, author. | Racaniello, V. R. (Vincent R.), author. | Rall, Glenn F., author. | Hatziioannou, Theodora, author. | Skalka, Anna Marie, author.
Title: Principles of virology / Jane Flint, Department of Molecular Biology, Princeton University, Princeton, New Jersey, Vincent R. Racaniello, Department of Microbiology & Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, Glenn F. Rall, Fox Chase Cancer Center, Philadelphia, Pennsylvania, Theodora Hatziioannou, The Rockefeller University, New York, New York, Anna Marie Skalka, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Description: Fifth edition. | Washington, DC : American Society for Microbiology [2020] ; Hoboken, NJ : Wiley, [2020] | Includes bibliographical references and index. | Contents: volume 1. Molecular biology—volume 2. Pathogenesis and control.
Identifiers: LCCN 2020013722 (print) | LCCN 2020013723 (ebook) | ISBN 9781683670322 (set) | ISBN 9781683672845 (v. 1 ; paperback) | ISBN 9781683672852 (v. 2 ; paperback) | ISBN 9781683672821 (v. 1 ; adobe pdf) | ISBN 9781683673606 (v. 1 ; epub) | ISBN 9781683672838 (v. 2 ; adobe pdf) | ISBN 9781683673590 (v. 2 ; epub) | ISBN 9781683670339 (adobe pdf) | ISBN 9781683673583 (epub)
Subjects: LCSH: Virology.
Classification: LCC QR360 .P697 2020 (print) | LCC QR360 (ebook) | DDC 616.9/101—dc23
LC record available at https://lccn.loc.gov/2020013722
LC ebook record available at https://lccn.loc.gov/2020013723
Illustrations and illustration concepting: Patrick Lane, ScEYEnce Studios
Cover image: Visual Science
Cover and interior design: Susan Brown Schmidler
We dedicate this book to the students, current and future scientists, physicians, and all those with an interest in the field of virology, for whom it was written.We kept them ever in mind.
We also dedicate it to our families:Jonn, Gethyn, and Amy LeedhamDoris, Aidan, Devin, and NadiaEileen, Kelsey, and AbigailPaul, Stefan, and EveRudy, Jeannie, and Chris
Oh, be wiser thou!Instructed that true knowledge leads to love.WILLIAM WORDSWORTHLines left upon a Seat in a Yew-tree1888
About the Instructor Companion Website
This book is accompanied by a companion website:
www.wiley.com/go/flint/pov5
The website includes:
PowerPoints of figures
Author podcasts
Study Questions and Answers
Preface
The enduring goal of scientific endeavor, as of all human enterprise, I imagine, is to achieve an intelligible view of the universe. One of the great discoveries of modern science is that its goal cannot be achieved piecemeal, certainly not by the accumulation of facts. To understand a phenomenon is to understand a category of phenomena or it is nothing. Understanding is reached through creative acts.
A. D. HERSHEY
Carnegie Institution Yearbook 65
All five editions of this textbook have been written according to the authors’ philosophy that the best approach to teaching introductory virology is by emphasizing shared principles. Studying the common steps of the viral reproductive cycle, illustrated with a set of representative viruses, and considering mechanisms by which these viruses can cause disease provides an integrated overview of the biology of these infectious agents. Such knowledge cannot be acquired by learning a collection of facts about individual viruses. Consequently, the major goal of this book is to define and illustrate the basic principles of virus biology.
In this information-rich age, the quantity of data describing any given virus can be overwhelming, if not indigestible, for student and expert alike. The urge to write more and more about less and less is the curse of reductionist science and the bane of those who write textbooks meant to be used by students. In the fifth edition, we continue to distill information with the intent of extracting essential principles, while providing descriptions of how the information was acquired and tools to encourage our readers’ exploration of the primary literature. Boxes are used to emphasize major principles and to provide supplementary material of relevance, from explanations of terminology to descriptions of trailblazing experiments. Our goal is to illuminate process and strategy as opposed to listing facts and figures. In an effort to make the book readable, we have been selective in our choice of viruses that are used as examples. The encyclopedic Fields’ Virology [Knipe DM, Howley PM (ed). 2020. Fields Virology, 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA] is recommended as a resource for detailed reviews of specific virus families.
What’s New
This edition is marked by a welcome addition to the author team. Our new member, Theodora Hatziioannou, brings expertise in retrovirology, entry, and intrinsic immunity, as well as authority regarding ancient Greek mythology and philosophy that the attentive reader will see is generously sprinkled throughout the text.
We have added an important new chapter in Volume II, “Therapeutic Viruses.” While the majority of the chapters define how viruses reproduce and cause mayhem to both cell and host, this new chapter turns the tables to discuss how viruses can be beneficial to eliminate tumor cells, deliver therapeutic genes to specific cells, and expand our arsenal of vaccines for prevention of virus-mediated diseases.
The authors continually strive to make this text accessible and relevant to our readers, many of whom are undergraduates, graduate students, and postdoctoral fellows. Consequently, for this edition, we enlisted the aid of more than twenty of these trainees to provide guidance and commentary on our chapters and ensure that concepts are clearly explained and that the text is compelling to read. This unique group of editors has been invaluable in the design of all of our fully reworked and up-to-date chapters and appendices, and we extend a particular thank-you to them for sharing their perspectives.
A new feature is the inclusion of a set of study questions and/or, in some cases, puzzles, as aids to ensure that the key principles are evident within each chapter. This section complements the Principles that begin each chapter, focusing on unifying core concepts.
Finally, although the SARS-CoV-2 pandemic began as we were preparing to go to press, we have included additions to relevant chapters on the epidemiology, emergence, and replication of this global scourge, as well as some hopeful information concerning vaccine development. What is apparent is that, now more than ever, an appreciation of how viruses impact their hosts is not just an academic pursuit, but rather literally a matter of life and death. We extend our gratitude to all those who serve in patient care settings.
Principles Taught in Two Distinct, but Integrated Volumes
Volume I covers the molecular biology of viral reproduction, and Volume II focuses on viral pathogenesis, control of virus infections, and virus evolution. The organization into two volumes follows a natural break in pedagogy and provides considerable flexibility and utility for students and teachers alike. The two volumes differ in content but are integrated in style and presentation. In addition to updating the chapters and appendices for both volumes, we have organized the material more efficiently, and as noted above, added a new chapter that we believe reflects an exciting direction for the field. Links to Internet resources such as websites, podcasts, blog posts, and movies are provided within each chapter; the digital edition provides one-click access to these materials.
As in our previous editions, we have tested ideas for inclusion in the text in our own classes. We have also received constructive comments and suggestions from other virology instructors and their students. Feedback from our readers was particularly useful in finding typographical errors, clarifying confusing or complicated illustrations, and pointing out inconsistencies in content.
For purposes of readability, references are not included within the text; each chapter ends with an updated list of relevant books, review articles, and selected research papers for readers who wish to pursue specific topics. New to this edition are short descriptions of the key messages from each of the cited papers of special interest. Finally, each volume has a general glossary of essential terms.
These two volumes outline and illustrate the strategies by which all viruses reproduce, how infections spread within a host, and how they are maintained in populations. We have focused primarily on animal viruses, but have drawn insights from studies of viruses that reproduce in plants, bacteria, and archaea.
Volume I: The Science of Virology and the Molecular Biology of Viruses
This volume examines the molecular processes that take place in an infected host cell. Chapter 1 provides a general introduction and historical perspective, and includes descriptions of the unique properties of viruses. The unifying principles that are the foundations of virology, including the concept of a common strategy for viral propagation, are then described. The principles of the infectious cycle, descriptions of the basic techniques for cultivating and assaying viruses, and the concept of the single-step growth cycle are presented in Chapter 2.
The fundamentals of viral genomes and genetics, and an overview of the surprisingly limited repertoire of viral strategies for genome replication and mRNA synthesis, are topics of Chapter 3. The architecture of extracellular virus particles in the context of providing both protection and delivery of the viral genome in a single vehicle is considered in Chapter 4. Chapters 5 to 13 address the broad spectrum of molecular processes that characterize the common steps of the reproductive cycle of viruses in a single cell, from decoding genetic information to genome replication and production of progeny virions. We describe how these common steps are accomplished in cells infected by diverse but representative viruses, while emphasizing common principles. Volume I concludes with a chapter that presents an integrated description of cellular responses to illustrate the marked, and generally irreversible, impact of virus infection on the host cell.
The appendix in Volume I provides concise illustrations of viral reproductive cycles for members of the main virus families discussed in the text. It is intended to be a reference resource when reading individual chapters and a convenient visual means by which specific topics may be related to the overall infectious cycles of the selected viruses.
Volume II: Pathogenesis, Control, and Evolution
This volume addresses the interplay between viruses and their host organisms. In Chapter 1, we introduce the discipline of epidemiology, and consider basic aspects that govern how the susceptibility of a population is controlled and measured. Physiological barriers to virus infections, and how viruses spread in a host, and to other hosts, are the topics of Chapter 2. The early host response to infection, comprising cell-autonomous (intrinsic) and innate immune responses, are the topics of Chapter 3, while the next chapter considers adaptive immune defenses, which are tailored to the pathogen, and immune memory. Chapter 5 focuses on the classical patterns of virus infection within cells and hosts, and the myriad ways that viruses cause illness. In Chapter 6, we discuss virus infections that transform cells in culture and promote oncogenesis (the formation of tumors) in animals. Next, we consider the principles underlying treatment and control of infection. Chapter 7 focuses on vaccines, and Chapter 8 discusses the approaches and challenges of antiviral drug discovery. In Chapter 9, the new chapter in this edition, we describe the rapidly expanding applications of viruses as therapeutic agents. The origin of viruses, the drivers of viral evolution, and host-virus conflicts are the subjects of Chapter 10. The principles of emerging virus infections, and humankind’s experiences with epidemic and pandemic viral infections, are considered in Chapter 11. Chapter 12 is devoted entirely to the “AIDS virus,” human immunodeficiency virus type 1, not only because it is the causative agent of the most serious current worldwide epidemic but also because of its unique and informative interactions with the human immune defenses. Volume II ends with a chapter on unusual infectious agents, viroids, satellites, and prions.
The Appendix of Volume II affords snapshots of the pathogenesis of common human viruses. This appendix has been completely re-envisioned in this edition, and now includes panels that define pathogenesis, vaccine and antiviral options, and the course of the infection through the human body. This consistent format should allow students to find information more easily, and compare properties of the selected viruses.
For some behind-the-scenes information about how the authors created the previous edition of Principles of Virology, see: http://bit.ly/Virology_MakingOf.
Acknowledgments
These two volumes of Principles could not have been composed and revised without help and contributions from many individuals. We are most grateful for the continuing encouragement from our colleagues in virology and the students who use the text. Our sincere thanks also go to colleagues who have taken considerable time and effort to review the text in its evolving manifestations. Their expert knowledge and advice on issues ranging from teaching virology to organization of individual chapters and style were invaluable and are inextricably woven into the final form of the book.
We also are grateful to those who gave so generously of their time to serve as expert reviewers of individual chapters or specific topics in these two volumes: Siddharth Balachandran (Fox Chase Cancer Center), Paul Bieniasz (Rockefeller University), Christoph Seeger (Fox Chase Cancer Center), and Laura Steel (Drexel University College of Medicine). Their rapid responses to our requests for details and checks on accuracy, as well as their assistance in simplifying complex concepts, were invaluable.
As noted in “What’s New,” we benefited from the efforts of the students and postdoctoral fellows who provided critiques on our chapters and helped to guide our revisions: Pradeep Morris Ambrose, Ruchita Balasubramanian, Mariana Nogueira Batista, Pierre Michel Jean Beltran, Marni S. Crow, Qiang Ding, Florian Douam, Jenna M. Gaska, Laura J. Halsey, Eliana Jacobson, Orkide O. Koyuncu, Robert LeDesma, Rebecca Markham, Alexa McIntyre, Katelynn A. Milora, Laura A. M. Nerger, Morgan Pantuck, Chen Peng, Katrien Poelaert, Daniel Poston, Anagha Prasanna, Pavithran T. Ravindran, Inna Ricardo-Lax, Fabian Schmidt, Andreas Solomos, Nikhila Shree Tanneti, Sharon M. Washio, Riley M. Williams, and Kai Wu.
Since the inception of this work, our belief has been that the illustrations must complement and enrich the text. The illustrations are an integral part of the text, and credit for their execution goes to the knowledge, insight, and artistic talent of Patrick Lane of ScEYEnce Studios. A key to common figure elements is provided following the “About the Authors” section. As noted in the figure legends, many could not have been completed without the help and generosity of numerous colleagues who provided original images. Special thanks go to those who crafted figures or videos tailored specifically to our needs, or provided multiple pieces in this latest edition: Jônatas Abrahão (Universidade Federal de Minas Gerais), Mark Andrake (Fox Chase Cancer Center), Irina Arkhipova (Marine Biological Laboratory, Woods Hole), Brian Baker (University of Notre Dame), Ben Beaden (Australia Zoo, Queensland), Paul Bieniasz (Rockefeller University), Kartik Chandran (Albert Einstein College of Medicine), Elliot Lefkowitz (University of Alabama), Joseph Pogliano (University of California, San Diego), B.V. Venkatar Prasad and Liya Hu (Baylor College of Medicine), Bonnie Quigley (University of the Sunshine Coast, Australia), Jason Roberts (Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, Australia), Michael Rout (Rockefeller University), and Nuria Verdaguer (Molecular Biology Institute of Barcelona, CSIC).
