116,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
The foundational textbook on the study of virology
Basic Virology, 4th Edition cements this series’ position as the leading introductory virology textbook in the world. It’s easily read style, outstanding figures, and comprehensive coverage of fundamental topics in virology all account for its immense popularity.
This undergraduate-accessible book covers all the foundational topics in virology, including:
- The basics of virology
- Virological techniques
- Molecular biology
- Pathogenesis of human viral disease
The 4th edition includes new information on the SARS, MERS and COVID-19 coronaviruses, hepatitis C virus, influenza virus, as well as HIV and Ebola. New virological techniques including bioinformatics and advances in viral therapies for human disease are also explored in-depth. The book also includes entirely new sections on metapneumoviruses, dengue virus, and the chikungunya virus.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 1179
Veröffentlichungsjahr: 2021
Ähnliche
Table of Contents
Cover
Dedication Page
Title Page
Copyright Page
Preface to the First Edition
Preface to the Second Edition
Preface to the Third Edition
Preface to the Fourth Edition
Acknowledgments
PART I: Virology and Viral Disease
CHAPTER 1: Introduction – The Impact of Viruses on Our View of Life
THE SCIENCE OF VIROLOGY
QUESTIONS FOR CHAPTER 1
CHAPTER 2: An Outline of Virus Replication and Viral Pathogenesis
VIRUS REPLICATION
PATHOGENESIS OF VIRAL INFECTION
QUESTIONS FOR CHAPTER 2
CHAPTER 3: Virus Disease in Populations and Individual Animals
THE NATURE OF VIRUS RESERVOIRS
VIRUSES IN POPULATIONS
ANIMAL MODELS TO STUDY VIRAL PATHOGENESIS
QUESTIONS FOR CHAPTER 3
CHAPTER 4: Patterns of Some Viral Diseases of Humans
THE DYNAMICS OF HUMAN–VIRUS INTERACTIONS
PATTERNS OF SPECIFIC VIRAL DISEASES OF HUMANS
SOME VIRAL INFECTIONS TARGETING SPECIFIC ORGAN SYSTEMS
QUESTIONS FOR CHAPTER 4
Problems PART I
Additional Reading for Part I
PART II: Basic Properties of Viruses and Virus–Cell Interaction
CHAPTER 5: Virus Structure and Classification
THE FEATURES OF A VIRUS
CLASSIFICATION SCHEMES
THE VIROSPHERE
THE HUMAN VIROME
QUESTIONS FOR CHAPTER 5
CHAPTER 6: The Beginning andEnd of the Virus Replication Cycle
OUTLINE OF THE VIRUS REPLICATION CYCLE
VIRAL ENTRY
LATE EVENTS IN VIRAL INFECTION: CAPSID ASSEMBLY AND VIRION RELEASE
QUESTIONS FOR CHAPTER 6
CHAPTER 7: The Innate Immune Response
HOST CELL–BASED DEFENSES AGAINST VIRUS REPLICATION
THE ADAPTIVE IMMUNE RESPONSE AND THE LYMPHATIC SYSTEM
CONTROL AND DYSFUNCTION OF IMMUNITY
MEASUREMENT OF THE IMMUNE REACTION
QUESTIONS FOR CHAPTER 7
CHAPTER 8: Strategies to Protect Against and Combat Viral Infection
VACCINATION – INDUCTION OF IMMUNITY TO PREVENT VIRUS INFECTION
EUKARYOTIC CELL‐BASED DEFENSES AGAINST VIRUS REPLICATION
ANTIVIRAL DRUGS
BACTERIAL ANTIVIRAL SYSTEMS – RESTRICTION ENDONUCLEASES
QUESTIONS FOR CHAPTER 8
Problems PART II
Additional Reading for Part II
PART III: Working with Virus
CHAPTER 9: Visualization and Enumeration of Virus Particles
USING THE ELECTRON MICROSCOPE TO STUDY AND COUNT VIRUSES
ATOMIC FORCE MICROSCOPY – A RAPID AND SENSITIVE METHOD FOR VISUALIZATION OF VIRUSES AND INFECTED CELLS, POTENTIALLY IN REAL TIME
INDIRECT METHODS FOR “COUNTING” VIRUS PARTICLES
QUESTIONS FOR CHAPTER 9
CHAPTER 10: Replicating and Measuring Biological Activity of Viruses
CELL CULTURE TECHNIQUES
THE OUTCOME OF VIRUS INFECTION IN CELLS
MEASUREMENT OF THE BIOLOGICAL ACTIVITY OF VIRUSES
QUESTIONS FOR CHAPTER 10
CHAPTER 11: Physical and Chemical Manipulation of the Structural Components of Viruses
VIRAL STRUCTURAL PROTEINS
CHARACTERIZING VIRAL GENOMES
QUESTIONS FOR CHAPTER 11
CHAPTER 12: Characterization of Viral Products Expressed in the Infected Cell
CHARACTERIZATION OF VIRAL PROTEINS IN THE INFECTED CELL
DETECTING AND CHARACTERIZING VIRAL NUCLEIC ACIDS IN INFECTED CELLS
USE OF MICROARRAY TECHNOLOGY FOR GETTING A COMPLETE PICTURE OF THE EVENTS OCCURRING IN THE INFECTED CELL
QUESTIONS FOR CHAPTER 12
CHAPTER 13: Viruses Use Cellular Processes to Express their GeneticInformation
PROKARYOTIC DNA REPLICATION IS AN ACCURATE ENZYMATIC MODEL FOR THE PROCESS GENERALLY
EXPRESSION OF mRNA
PROKARYOTIC TRANSCRIPTION
EUKARYOTIC TRANSCRIPTION
THE MECHANISM OF PROTEIN SYNTHESIS
QUESTIONS FOR CHAPTER 13
Problems PART III
Additional Reading for Part III
PART IV: Replication Patterns of Specific Viruses
CHAPTER 14: Replication of Positive‐Sense RNAViruses
RNA VIRUSES – GENERAL CONSIDERATIONS
REPLICATION OF POSITIVE‐SENSE RNA VIRUSES WHOSE GENOMES ARE TRANSLATED AS THE FIRST STEP IN GENE EXPRESSION
POSITIVE‐SENSE RNA VIRUSES ENCODING A SINGLE LARGE OPEN READING FRAME
POSITIVE‐SENSE RNA VIRUSES ENCODING MORE THAN ONE TRANSLATIONAL READING FRAME
REPLICATION OF PLANT VIRUSES WITH RNA GENOMES
REPLICATION OF BACTERIOPHAGES WITH RNA GENOMES
QUESTIONS FOR CHAPTER 14
CHAPTER 15: Replication Strategies of RNA Viruses Requiring RNA‐directed mRNA Transcription as the First Step in Viral Gene Expression
REPLICATION OF NEGATIVE‐SENSE RNA VIRUSES WITH A MONOPARTITE GENOME
NEGATIVE‐SENSE RNA VIRUSES WITH A MULTIPARTITE GENOME
OTHER NEGATIVE‐SENSE RNA VIRUSES WITH MULTIPARTITE GENOMES
VIRUSES WITH DOUBLE‐STRANDED RNA GENOMES
SUBVIRAL PATHOGENS
QUESTIONS FOR CHAPTER 15
CHAPTER 16: Replication Strategies of Small and Medium‐sized DNA Viruses
DNA VIRUSES EXPRESS GENETIC INFORMATION AND REPLICATE THEIR GENOMES IN SIMILAR, YET DISTINCT, WAYS
PAPOVAVIRUS REPLICATION
THE REPLICATION OF ADENOVIRUSES
REPLICATION OF SOME SINGLE‐STRANDED DNA VIRUSES
QUESTIONS FOR CHAPTER 16
CHAPTER 17: Replication of Some Nuclear‐replicating Eukaryotic DNA Viruses with Large Genomes
HERPESVIRUS REPLICATION AND LATENCY
BACULOVIRUS: AN INSECT VIRUS WITH IMPORTANT PRACTICAL USES IN MOLECULAR BIOLOGY
QUESTIONS FOR CHAPTER 17
CHAPTER 18: Replication of Cytoplasmic DNA Viruses and “Large” Bacteriophages
POXVIRUSES – DNA VIRUSES THAT REPLICATE IN THE CYTOPLASM OF EUKARYOTIC CELLS
REPLICATION OF “LARGE” DNA‐CONTAINING BACTERIOPHAGES
A GROUP OF ALGAL VIRUSES SHARES FEATURES OF ITS GENOME STRUCTURE WITH POXVIRUSES AND BACTERIOPHAGES
QUESTIONS FOR CHAPTER 18
CHAPTER 19: Retroviruses
RETROVIRUS FAMILIES AND THEIR STRATEGIES OF REPLICATION
MECHANISMS OF RETROVIRUS TRANSFORMATION
CELLULAR GENETIC ELEMENTS RELATED TO RETROVIRUSES
QUESTIONS FOR CHAPTER 19
CHAPTER 20: Human Immunodeficiency Virus Type 1 (HIV‐1) and Related Lentiviruses
HIV‐1 AND RELATED LENTIVIRUSES
THE ORIGIN OF HIV‐1 AND AIDS
HIV‐1 AND LENTIVIRAL REPLICATION
DESTRUCTION OF THE IMMUNE SYSTEM BY HIV‐1
QUESTIONS FOR CHAPTER 20
CHAPTER 21: Hepadnaviruses: Variations on the Retrovirus Theme
THE VIRION AND THE VIRAL GENOME
THE VIRAL REPLICATION CYCLE
THE PATHOGENESIS OF HEPATITIS B VIRUS
PREVENTION AND TREATMENT OF HEPATITIS B VIRUS INFECTION
HEPATITIS DELTA VIRUS
A PLANT “HEPADNAVIRUS”: CAULIFLOWER MOSAIC VIRUS
THE EVOLUTIONARY ORIGIN OF HEPADNAVIRUSES
QUESTIONS FOR CHAPTER 21
Problems PART IV
Additional Reading for Part IV
VIRUS RESOURCES ON THE INTERNET
PART V: Molecular Genetics of Viruses
CHAPTER 22: The Molecular Genetics of Viruses
MUTATIONS IN GENES AND RESULTING CHANGES TO PROTEINS
ANALYSIS OF MUTATIONS
ISOLATION OF MUTANTS
A TOOL KIT FOR MOLECULAR VIROLOGISTS
LOCATING SITES OF RESTRICTION ENDONUCLEASE CLEAVAGE ON THE VIRAL GENOME – RESTRICTION MAPPING
CLONING VECTORS
DIRECTED MUTAGENESIS OF VIRAL GENES
GENERATION OF RECOMBINANT VIRUSES
QUESTIONS FOR CHAPTER 22
CHAPTER 23: Molecular Pathogenesis
AN INTRODUCTION TO THE STUDY OF VIRAL PATHOGENESIS
ANIMAL MODELS
METHODS FOR THE STUDY OF PATHOGENESIS
CHARACTERIZATION OF THE HOST RESPONSE
QUESTIONS FOR CHAPTER 23
CHAPTER 24: Viral Bioinformatics
BIOINFORMATICS
BIOLOGICAL DATABASES
BIOLOGICAL APPLICATIONS
SYSTEMS BIOLOGY AND VIRUSES
VIRAL INTERNET RESOURCES
QUESTIONS FOR CHAPTER 24
CHAPTER 25: Viruses and the Future – Problems and Promises
CLOUDS ON THE HORIZON – EMERGING DISEASE
WHAT ARE THE PROSPECTS OF USING MEDICAL TECHNOLOGY TO ELIMINATE SPECIFIC VIRAL AND OTHER INFECTIOUS DISEASES?
SILVER LININGS – VIRUSES AS THERAPEUTIC AGENTS
WHY STUDY VIROLOGY?
QUESTIONS FOR CHAPTER 25
Problems PART V
Additional Reading for Part V
Appendix – Resource Center
BOOKS OF HISTORICAL AND BASIC VALUE
BOOKS ON VIROLOGY
MOLECULAR BIOLOGY AND BIOCHEMISTRY TEXTS
DETAILED SOURCES
SOURCES FOR EXPERIMENTAL PROTOCOLS
THE INTERNET
Technical Glossary
Index
End User License Agreement
List of Tables
Chapter 2
Table 2.1 Some viruses that replicate in cells of the immune system.
Table 2.2 Some examples of viral cytopathic effect.
Chapter 3
Table 3.1 Some pathogenic viruses, their vectors or routes of spread, and the...
Chapter 4
Table 4.1 Some viruses infecting humans.
Chapter 5
Table 5.1 Classification of viruses according to the ICTV.
Table 5.2 The Baltimore classification scheme for viruses.
Chapter 6
Table 6.1 Some cellular receptors for selected animal viruses.
Table 6.2 Some
E. coli
bacteriophage receptors.
Chapter 7
Table 7.1 Some antiviral proteins induced or activated by interferon.
Chapter 8
Table 8.1 Some human viral vaccines.
Table 8.2 Some targets for antiviral drugs.
Chapter 10
Table 10.1 An example of a set of dilutions for a plaque assay.
Table 10.2 An example of a quantal assay for virus infectivity.
Chapter 11
Table 11.1 Gel fractionation of the poliovirus’s four capsid proteins.
Table 11.2 Protein composition of the HSV‐1 capsid.
Chapter 14
Table 14.1 Genomic structure of some positive‐sense RNA viruses infecting euk...
Chapter 15
Table 15.1 Similarities and differences of orthomyxovirus and paramyxovirus.
Table 15.2 Some members of the Bunyavirales and their vectors.
Chapter 17
Table 17.1 Some genetic functions encoded by herpes simplex virus type 1.
Chapter 19
Table 19.1 Selected examples of oncogenes acquired by retroviruses.
Table 19.2 Bacterial transposons.
Table 19.3 Some retroelements of eukaryotic cells.
Chapter 20
Table 20.1 Table of lentiviruses showing host species.
Chapter 22
Table 22.1 Some viral vector systems.
Chapter 23
Table 23.1 Differences in neuroinvasiveness of HSV‐1 strains.
Table 23.2 Differences in susceptibility of mouse strains to HSV‐1 infection.
List of Illustrations
Chapter 1
Figure 1.1 A phylogenetic tree of selected species from the three domains of...
Figure 1.2 A phylogenetic tree of selected eukaryotic and archaeal species a...
Chapter 2
Figure 2.1 Dimensions and features of “typical” (a) animal, (b) plant, and (...
Figure 2.2 The virus replication cycle. Most generally, virus replication ca...
Figure 2.3 The pathogenesis of virus infection. Typically, infection is foll...
Figure 2.4 Sites of virus entry in a human. These or similar sites apply to ...
Chapter 3
Figure 3.1 Some transmission routes of specific viruses from their source (r...
Figure 3.2 Occurrence of respiratory illness in an arctic community (Spitzbe...
Figure 3.3 Fictionalized timeline of the spread of SARS virus following its ...
Figure 3.4 The course of experimental poxvirus infection in laboratory mice....
Figure 3.5 Visualization of rabies virus–infected neurons in experimentally ...
Figure 3.6 Analysis of the establishment and maintenance of latent HSV infec...
Chapter 4
Figure 4.1 Virus maintenance in small and large populations. (a) In a small ...
Figure 4.2 Examples of virus infection of specific organs or organ systems. ...
Chapter 5
Figure 5.1 A scale of dimensions for biologists. The wavelength of a photon ...
Figure 5.2 The structure and relative sizes of a number of (a) DNA and (b) R...
Figure 5.3 Crystallographic structure of a simple icosahedral virus. (a) The...
Figure 5.4 The structure of a simple icosahedral virus. (a) A space‐filling ...
Figure 5.5 The virosphere. Classification of a major portion of the currentl...
Chapter 6
Figure 6.1 The surface of a “typical” animal cell. The lipid bilayer plasma ...
Figure 6.2 Schematic of receptor‐mediated endocytosis utilized by rhinovirus...
Figure 6.3 (a) The two basic modes of entry of an enveloped animal virus int...
Figure 6.4 Entry of T4 bacteriophage DNA into an
E. coli
cell. Initial attac...
Figure 6.5 Expression of a varicella zoster virus protein following transfec...
Figure 6.6 Assembly of the helical
tobacco mosaic virus
(
TMV
). Steps in the ...
Figure 6.7 Assembly of the phage P22 capsid and maturation by insertion of v...
Figure 6.8 Insertion of glycoproteins into the cell's membrane structures an...
Figure 6.9 Visualization of the budding of an enveloped virion from the plas...
Figure 6.10 The envelopment and egress of herpesvirus. Electron micrographs ...
Chapter 7
Figure 7.1 Schematic representation showing differences in the intensity and...
Figure 7.2 The cascade of events leading to expression of interferon (IFN) a...
Figure 7.3 The human lymphatic system. The lymphatic system is the principal...
Figure 7.4 T and B cells in immunity. T lymphocytes play the central coordin...
Figure 7.5 The antigenic structure of a protein. Specific groups of amino ac...
Figure 7.6 The processing of a foreign antigen and stimulation of the immune...
Figure 7.7 The clonal selection of B lymphocytes. Only the B lymphocytes rea...
Figure 7.8 Immune memory. The first exposure to an antigen results in the pr...
Figure 7.9 The maturational cascade of serum complement proteins upon bindin...
Figure 7.10 An enzyme‐linked immunosorbent assay (ELISA): the method of usin...
Figure 7.11 Antibody neutralization of virus infectivity. Specific types of ...
Figure 7.12 The hemagglutination inhibition assay for measuring antibody aga...
Chapter 8
Figure 8.1 The structure of some currently effective antiviral drugs.
Chapter 9
Figure 9.1 A schematic comparison of light and electron microscopes. The pri...
Figure 9.2 Shadowing specimens for viewing in the electron microscope. (a) A...
Figure 9.3 Computer‐enhanced three‐dimensional reconstruction of viral capsi...
Figure 9.4 Atomic force microscopy was used to visualize the protein capsid ...
Chapter 10
Figure 10.1 Generating a primary cell culture. Tissue is surgically removed ...
Figure 10.2 The progression of cells in culture from primary to transformed ...
Figure 10.3 Apoptosis versus necrosis in cell death.
Figure 10.4 HSV‐induced changes in the properties of actin microfilaments of...
Figure 10.5 Visualization of virus plaques. Under appropriate conditions, vi...
Figure 10.6 Rabbitpox virus pocks on the
chorioallantoic membrane
(CAM) of a...
Figure 10.7 Some representative morphologies of rat fibroblast cells (F‐111)...
Figure 10.8 Serial 10‐fold dilutions of HSV to determine the titer of virus ...
Figure 10.9 Quantal (endpoint dilution) assay of HSV in tissue culture wells...
Figure 10.10 Graphic analysis of the data from Figure 10.8. The percentage o...
Chapter 11
Figure 11.1 Equilibrium density gradient centrifugation of virus‐infected ce...
Figure 11.2 Differential centrifugation to purify virions. Infected cells ar...
Figure 11.3 Denaturing gel electrophoresis of proteins. If proteins are gent...
Figure 11.4 Electrophoretic fractionation of the capsid proteins isolated fr...
Figure 11.5 Electrophoretic fractionation of the capsid proteins isolated fr...
Figure 11.6 The famous Kleinschmidt electron micrograph of phage T4 DNA extr...
Figure 11.7 Enzymatic sequencing of DNA. The generation of overlapping oligo...
Figure 11.8
High‐throughput sequencing
(
HTS
) of DNA. Several different...
Figure 11.9 Amplification of DNA with the
polymerase chain reaction
(
PCR
). (...
Figure 11.10 Real‐time PCR amplification of globin DNA in blood macrophages....
Chapter 12
Figure 12.1 Changes in the proteins synthesized in virus‐infected cells with...
Figure 12.2 The structure of an antibody molecule, IgG. This molecule is mad...
Figure 12.3 Generation of monoclonal antibodies by making hybridoma cells by...
Figure 12.4 Outline of immunofluorescence as a means of detecting and locali...
Figure 12.5 Confocal microscopy to detect co‐localization of antigens. (a) T...
Figure 12.6 Human thymocytes in organ culture were mock infected or infected...
Figure 12.7 Detection and isolation of proteins reactive with a specific ant...
Figure 12.8 Use of immunoaffinity chromatography to isolate HSV envelope pro...
Figure 12.9 Saliva from recently HIV‐infected people, individuals with long‐...
Figure 12.10 Different viral mRNA molecules are encoded by different regions...
Figure 12.11
In situ
hybridization of human neurons latently infected with H...
Figure 12.12
In situ
hybridization of sections of suckling mice infected wit...
Figure 12.13 Characterization of isolated viral mRNA by
in vitro
translation
Figure 12.14 The application of microarrays or the study of viral products p...
Chapter 13
Figure 13.1 The enzymes and other proteins associated with DNA around a grow...
Figure 13.2 Initiation of HSV DNA replication. This process is virtually ide...
Figure 13.3 The
E. coli
lac operon. The promoter is always “on,” but normall...
Figure 13.4 The bacterial RNA polymerase molecule. The enzyme is made up of ...
Figure 13.5 The multistep process of transcription initiation at a eukaryoti...
Figure 13.6 The flexibility of DNA allows transcription factors to bind at s...
Figure 13.7 Control of eukaryotic transcription. (a) The availability of the...
Figure 13.8 Steps involved in transcription and posttranscriptional modifica...
Figure 13.9 A “high‐resolution” example of mRNA processing. The sequence of ...
Figure 13.10 Some splicing patterns seen in the generation of eukaryotic vir...
Figure 13.11 Posttranscriptional regulation of eukaryotic mRNA. Once transcr...
Figure 13.12 Initiation of eukaryotic translation. Note the initiation compl...
Figure 13.13 Initiation of translation of a prokaryotic mRNA. This can occur...
Chapter 14
Figure 14.1 Some general features of viruses containing RNA genomes that use...
Figure 14.2 (a) Poliovirus, a typical picornavirus. The 30‐nm‐diameter icosa...
Figure 14.3 The poliovirus replication cycle. The schematic representation i...
Figure 14.4 The steps in the assembly of the poliovirus virion. Precursor pr...
Figure 14.5 The yellow fever virus (a flavivirus) and its genome. This flavi...
Figure 14.6 Sindbis virus – a typical togavirus. The virion (60–70 nm in dia...
Figure 14.7 The early stages of Sindbis virus infection. (a) The first step ...
Figure 14.8 (a) The replication of Sindbis virus genome, and generation of t...
Figure 14.9 A schematic representation of the coronavirus virion. This is th...
Figure 14.10 The replication cycle of a coronavirus. Replication is entirely...
Figure 14.11 The approximately 25‐nm‐diameter icosahedral capsid of positive...
Figure 14.12 Coupled transcription–translation of bacteriophage Qβ RNA resul...
Chapter 15
Figure 15.1 The vesicular stomatitis virus (VSV) virion. All rhabdoviruses h...
Figure 15.2 The VSV replication cycle. (a) Early events in infection begin w...
Figure 15.3 A higher‐resolution schematic of the generation of positive‐sens...
Figure 15.4 The genetic map and virion structure of Sendai virus, a typical ...
Figure 15.5 The structure of influenza virus A. The virion is about 120 nm i...
Figure 15.6 An outline of the replication cycle of influenza. Following viru...
Figure 15.7 Antigenic changes in the surface glycoproteins of influenza A vi...
Figure 15.8 The bunyavirus virion. The three ribonucleoprotein (RNP) segment...
Figure 15.9 The ambisense strategy of gene expression exhibited by some buny...
Figure 15.10 The 60‐nm‐diameter human reovirus with its double shell. The 10...
Figure 15.11 The reovirus replication cycle. Virus attachment is followed by...
Figure 15.12 The potato spindle tuber viroid genome. Various pathogenic stra...
Figure 15.13 Prion‐specific protein.
Chapter 16
Figure 16.1 Polyomavirus and the genetic and transcript map of SV40 virus. (...
Figure 16.2 The replication cycle of SV40 virus in a permissive cell. The re...
Figure 16.3 The replication of SV40 DNA. The closed circular DNA has no end ...
Figure 16.4 Representation of the two steps in transformation of a nonpermis...
Figure 16.5 The human papillomavirus 16 (HPV‐16) genome. The 7‐kb circular g...
Figure 16.6 The formation of a wart by cell proliferation caused by infectio...
Figure 16.7 The genetic and transcription map of the 30‐kb adenovirus genome...
Figure 16.8 Adenovirus DNA replication. The 5′ ends of the viral genome have...
Figure 16.9 The 5000‐nucleotide (nt) linear genome of adeno‐associated virus...
Figure 16.10 The capsid structure and compressed genome of bacteriophage ΦX1...
Chapter 17
Figure 17.1 Electron micrograph of an enveloped HSV‐1 virion revealing speci...
Figure 17.2 The HSV‐1 genetic and transcription map. Specific features of th...
Figure 17.3 The programmed cascade of HSV transcription at different stages ...
Figure 17.4 The entry of HSV‐1 into a cell for the initiation of infection. ...
Figure 17.5 The HSV‐1 productive and latent infection cycles. In productive ...
Figure 17.6 Replication and encapsidation of viral genomes. (a) HSV DNA init...
Figure 17.7 Immune fluorescence analysis of the rearrangement of nuclear str...
Figure 17.8 Maturation of the HSV capsid and its envelopment by tegument and...
Figure 17.9 The “decision” made by HSV upon infection of epidermal tissue en...
Figure 17.10 The expression of HSV transcripts during latent infection and r...
Figure 17.11 The Epstein–Barr virus (EBV) genome and the latency transcripts...
Chapter 18
Figure 18.1 The vaccinia virus virion. The structure of poxviruses is the mo...
Figure 18.2 The replication cycle of vaccinia virus. Following viral attachm...
Figure 18.3 Replication of poxvirus DNA. The covalently closed, circular gen...
Figure 18.4 The structure and genetic map of T7 bacteriophage. (a) The 40‐kb...
Figure 18.5 The genetic map and structure of bacteriophage T4. By convention...
Figure 18.6 Rolling circle replication and packaging of phage T4 DNA. The pr...
Figure 18.7 Time of appearance of various functions encoded by T4 bacterioph...
Figure 18.8 The assembly of T4 bacteriophage. Note that assembly of the phag...
Figure 18.9 The bacteriophage λ genetic map. Specific clustered functions ar...
Figure 18.10 The earliest events in the infection of a bacteria by phage λ. ...
Figure 18.11 A phylogenetic tree of selected large‐DNA‐containing virus fami...
Chapter 19
Figure 19.1 The structures of an oncornavirus and a mature lentivirus. Virio...
Figure 19.2 Genetic maps of various retroviruses. Specific examples are disc...
Figure 19.3 The replication cycle of a typical retrovirus. (1) Adsorption an...
Figure 19.4 The detailed mechanism for formation of retroviral cDNA from vir...
Figure 19.5 Splicing patterns of various retrovirus RNAs to generate subgeno...
Figure 19.6 Cell division and oncogenes. (a) In the normal cell, division is...
Figure 19.7 The genomic structure of yeast Ty1. The similarity to a retrovir...
Chapter 20
Figure 20.1 The HIV‐1 genome, viral particle, and transcripts. The figure sh...
Figure 20.2 HIV‐1 entry in detail. HIV‐1 binds cell surface CD4 via its surf...
Figure 20.3 The HIV‐1 life cycle. After receptor‐mediated membrane fusion at...
Figure 20.4 Vif and APOBEC action. In the absence of effective HIV‐1 Vif pro...
Figure 20.5 Tat activation of HIV‐1 transcription. A tripartite complex cons...
Figure 20.6 Rev binds to the
Rev response element
(RRE) to mediate nuclear e...
Figure 20.7 HIV‐1 Vpu protein blocks the antiviral effect of tetherin. In th...
Figure 20.8 Nef and Vpu downregulate CD4 expression and Nef downregulates MH...
Figure 20.9 The pathogenesis of HIV infection leading to AIDS. Acute infecti...
Figure 20.10 Triphasic decay of HIV‐1 in plasma following initiation of effe...
Chapter 21
Figure 21.1 A diagram of the virion structure and a genomic and genetic map ...
Figure 21.2 The three RNAs of hepatitis delta virus found in infected liver ...
Figure 21.3 The genome of cauliflower mosaic virus. The three breaks in the ...
Chapter 22
Figure 22.1 The impact of molecular understanding of viral and host genes on...
Figure 22.2 Complementation. Neither of two mutant viruses shown can replica...
Figure 22.3 Replica plating of virus plaques to distinguish genotypes produc...
Figure 22.4 Mapping restriction endonuclease cleavage sites on a viral genom...
Figure 22.5 Three widely used cloning plasmids that replicate in
E. coli
. Th...
Figure 22.6 Isolation of a specific restriction fragment of viral DNA cloned...
Figure 22.7 A togavirus expression vector. Semliki Forest virus (a togavirus...
Figure 22.8 Directed mutagenesis of viral DNA. (a) Single‐stranded DNA conta...
Figure 22.9 Generating and isolating recombinant viruses. (a) As outlined in...
Figure 22.10 Generating a recombinant virus using CRISPR‐Cas gene editing. I...
Chapter 23
Figure 23.1 Construction of a transgenic mouse. The desired DNA (here, the h...
Figure 23.2 Use of SCID‐hu mice to study HIV pathogenesis. Human thymus–live...
Figure 23.3 Use of
ß‐galactosidase
(
ß‐gal
) as a report...
Figure 23.4 (a) MRI images of a mouse infected with HSV‐1 10 days post infec...
Figure 23.5 Use of a protein microarray to assay patient antibody reactivity...
Chapter 24
Figure 24.1 Growth of the genomic databases. Data displayed here are taken f...
Figure 24.2 Results of a BLAST Search for a Nucleotide Sequence. (a) Initial...
Figure 24.3 Random versus scale‐free networks. (a) A random network, in whic...
Figure 24.4 Yeast two‐hybrid detection system. Transformation vectors are cr...
Figure 24.5
Protein interaction map
(
PIM
) for the round worm,
Caenorhabditis
...
Figure 24.6 Host–virus protein interaction map of hepatitis C virus (HCV): t...
Chapter 25
Figure 25.1 Mortality from infectious diseases in the United States between ...
Guide
Cover Page
Dedication
Basic Virology
Copyright
Preface to the First Edition
Preface to the Second Edition
Preface to the Third Edition
Preface to the Fourth Edition
Acknowledgments
Table of Contents
Begin Reading
Appendix – Resource Center
Technical Glossary
Index
WILEY END USER LICENSE AGREEMENT
Pages
ii
iii
iv
xxi
xxii
xxiii
xxiv
xxv
xxvii
xxviii
1
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
43
44
45
46
49
50
51
52
54
55
56
57
58
59
60
61
62
63
65
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
145
147
148
149
151
153
155
156
157
158
159
160
161
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
433
434
435
437
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
499
500
501
503
504
505
506
507
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
533
In Memoriam
Edward K. Wagner
(May 4, 1940 to January 21, 2006)
It was one of those telephone calls that you do not want to receive. Each of us, that weekend in late January, heard of the untimely passing of our colleague, co‐author, collaborator, mentor, and friend, Ed Wagner. Ed will be remembered for his many contributions to the teaching of virology and for his research contributing to our understanding of the intricacies of the herpesviruses. From his graduate work at MIT, through his postdoctoral research at the University of Chicago, and on to his professorship at the University of California, Irvine, Ed was a passionate champion for the most rigorous and critical thinking and the most dedicated teaching, setting a standard for the discipline of virology. Beyond the laboratory and the classroom, Ed loved life to the fullest, with his family and friends. The last time we were together as a writing team, in the fall of 2005, we all remember an intense day of work in a conference room at UCI, followed by an evening of touring some of Ed’s favorite haunts in the Southern California coastal towns he called home. It is with those thoughts etched into our memories that we dedicate this edition of Basic Virology to Edward K. Wagner.
Basic Virology
Fourth Edition
Martinez “Marty” Hewlett
University of New MexicoTaos, NM, USA
David Camerini
Center for Virus ResearchUniversity of California, IrvineIrvine, CA, USA
David C. Bloom
Department of Molecular Genetics and MicrobiologyUniversity of FloridaGainesville, FL, USA
This fourth edition first published 2021© 2021 John Wiley & Sons, Inc.
Edition History:
1e; (1999, Wiley‐Blackwell) 2e; (2003, John Wiley & Sons), 3e; (2007, Wiley‐Blackwell).
All rights reserved. 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 or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Marty Hewlett, David Camerini, and David Bloom to be identified as the authors of this work has been asserted in accordance with law.
Registered OfficeJohn Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
Editorial OfficeBoschstr. 12, 69469 Weinheim, Germany
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand. Some content that appears in standard print versions of this book may not be available in other formats.
Limit of Liability/Disclaimer of Warranty
While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging‐in‐Publication DataNames: Hewlett, Martinez “Marty”, author. | Camerini, David, author. | Bloom, David (David C.), author.Title: Basic virology / Marty Hewlett, David Camerini, David Bloom.Description: Fourth edition. | Hoboken, NJ: Wiley‐Blackwell, 2021. | Preceded by: Basic virology / Edward K. Wagner … [et al.]. 3rd ed. 2008. | Includes bibliographical references and index.Identifiers: LCCN 2020026463 (print) | LCCN 2020026464 (ebook) | ISBN 9781119314059 (paperback) | ISBN 9781119314042 (adobe pdf) | ISBN 9781119314066 (epub)Subjects: MESH: Virus Diseases–virology | Viruses–pathogenicity | Virus Replication | Genome, ViralClassification: LCC QR360 (print) | LCC QR360 (ebook) | NLM WC 500 | DDC 579.2–dc23LC record available at https://lccn.loc.gov/2020026463LC ebook record available at https://lccn.loc.gov/2020026464
Cover Design: Wiley BlackwellCover Image: © Wah Chiu
Preface to the First Edition
Viruses have historically flickered in and out of the public consciousness. In the eight years since we finished the first edition of Basic Virology much has happened, both in the world and in virology, to fan the flames of this awareness.
In this period we have seen the development of a vaccine to protect women against human papilloma virus type 16. This major advance could well lead to a drastic reduction in the occurrence of cervical cancer. In addition, viruses as gene delivery vectors have increased the prospect of targeted treatments for a number of genetic diseases. The heightened awareness and importance of the epidemiological potential of viruses, in both natural and man‐caused outbreaks, have stimulated the search for both prophylactic and curative treatments.
However, the events of September 11, 2001, dramatically and tragically altered our perceptions. A new understanding of threat now pervades our public and private actions. In this new arena, viruses have taken center stage as the world prepares for the use of infectious agents such as smallpox in acts of bioterrorism.
Naturally occurring virological issues also continue to capture our attention. West Nile virus, originally limited to areas of North Africa and the Middle East, has utilized the modern transportation network to arrive in North America. Its rapid spread to virtually every state in the union has been both a public health nightmare and a vivid demonstration of the opportunism of infectious diseases. The continuing AIDS pandemic reminds us of the terrible cost of this opportunism. In addition, we are now faced with the very real prospect of the next pandemic strain of influenzas, perhaps derived from the avian H5N1 virus now circulating in wild and domestic birds.
It is against this backdrop of hope and concern that we have revised Basic Virology.
This book is based on more than 40 years in aggregate of undergraduate lectures on virology commencing in 1970 given by the coauthors (Wagner, Hewlett, Bloom, and Camerini) at the University of California, Irvine (UCI), the University of Arizona, and the University of Florida. The field of virology has matured and grown immensely during this time, but one of the major joys of teaching this subject continues to be the solid foundation it provides in topics running the gamut of the biological sciences. Concepts range from population dynamics and population ecology, through evolutionary biology and theory, to the most fundamental and detailed analyses of the biochemistry and molecular biology of gene expression and biological structures. Thus, teaching virology has been a learning tool for us as much as, or more than, it has been for our students.
Our courses are consistently heavily subscribed, and we credit that to the subject material, certainly not to any special performance tricks or instructional techniques. Participants have been mainly premedical students, but we have enjoyed the presence of other students bound for postgraduate studies, as well as a good number of those who are just trying to get their degree and get out of the “mill” and into the “grind.”
At UCI, in particular, the course had a tremendous enrollment (approximately 250 students per year) in the past 5–8 years, and it has become very clear that the material is very challenging for a sizable minority studying it. While this is good, the course was expanded in time to five hours per week for a 10‐week quarter to accommodate only those students truly interested in being challenged. Simply put, there is a lot of material to master, and mastery requires a solid working knowledge of basic biology and, most importantly, the desire to learn. This “experiment” has been very successful, and student satisfaction with the expanded course is, frankly, gratifying. To help students acquire such working knowledge, we have encouraged further reading. We have also included a good deal of reinforcement material to help students learn the basic skills of molecular biology and rudimentary aspects of immunology, pathology, and disease. Furthermore, we have incorporated numerous study and discussion questions at the end of chapters and sections to aid in discussion of salient points.
It is our hope that this book will serve as a useful text and source for many undergraduates interested in acquiring a solid foundation in virology and its relationship to modern biology. It is also hoped that the book may be of use to more advanced workers who want to make a quick foray into virology but who do not want to wade through the details present in more advanced works.
Preface to the Second Edition
The text retains our organizational format. As before, Part I concerns the interactions of viruses and host populations, Part II is about the experimental details of virus infection, Part III discusses the tools used in the study of viruses, and Part IV is a detailed examination of families and groupings of viruses. We have found, in our own teaching and in comments from colleagues, that this has been a useful approach. We have also kept our emphasis on problem solving and on the provision of key references for further study.
What is new in the second edition has been driven by changes in virology and in the tools used to study viruses. Some of these changes and additions include
a discussion of bioterrorism and the threat of viruses as weapons;
updated information on emerging viruses such as West Nile, and their spread;
the current state of HIV antiviral therapies;
discussions of viral genomics in cases where sequencing has been completed;
discussion of cutting‐edge technologies, such as atomic force microscopy and DNA microarray analysis; and
updated glossary and reference lists.
We have, throughout the revision, tried to give the most current understanding of the state of knowledge for a particular virus or viral process. We have been guided by a sense of what our students need in order to appreciate the complexity of the virological world and to come away from the experience with some practical tools for the next stages in their careers.
Preface to the Third Edition
It is with a true sense of our loss that the three of us sit in Irvine, California, Gainesville, Florida, and Taos, New Mexico, working toward completion of this edition. The absence of our friend and colleague, Ed Wagner, is all the more apparent as we write the preface to this latest edition of Basic Virology. In his spirit, we offer our colleagues and students this book that is our latest view of the field that Ed pursued with such passion and dedication.
In this new edition, we have attempted to bring the current state of our discipline into focus for students at the introductory and intermediate levels. To this end, we have done the job of providing the most current information, at this writing, for each of the subjects covered. We have also done some reorganization of the material. We have added three new chapters, in recognition of the importance of these areas to the study of viruses.
The book now includes a chapter devoted completely to HIV and the lentiviruses (Chapter 20), previously covered along with the retroviruses in general. Given that we continue to face the worldwide challenge of AIDS, we feel that this is an important emphasis.
You will also notice that this version now includes a Part V (“Viruses: New Approaches and New Problems”). This section begins with a consideration of the molecular tools used to study and manipulate viruses (Chapter 22), follows with coverage of viral pathogenesis at the molecular level (Chapter 23), and continues with a chapter dealing with viral genomics and bioinformatics (Chapter 24). We intend that these three chapters will give our students insight into the current threads of molecular and virological thinking. Part V concludes with our chapter on “Viruses and the Future” (Chapter 25), containing updated material on emerging viruses, including influenza, as well as viruses and nanotechnology.
A major change in this edition is the use of full‐color illustrations. We welcome this effort from our publisher, Blackwell Science, and hope that you find this adds value and utility to our presentation.
In conjunction with the expanded coverage, the Glossary has been revised. In addition, all of the references, both text and web‐based, have been reviewed and made current as of this writing.
Most of these changes were either finished or discussed in detail before Ed's untimely passing. As a result, we are proud to say that Basic Virology, Third Edition, bears the welcome imprint of the scientist/teacher who inspired the first one. We hope you agree and enjoy the fruits of this effort.
Marty Hewlett, Taos, NM, USADave Bloom, Gainesville, FL, USADavid Camerini, Irvine, CA, USA
Preface to the Fourth Edition
It seems like only yesterday that Ed and Marty spoke on the phone and said, in effect, “Let's do this thing,” giving birth to Basic Virology. And here we are, completing the revisions for the fourth edition of what we hope will remain a useful and relevant textbook for the teaching of introductory virology to undergraduates.
As it has from its very beginnings, the field of virology is changing at an astounding pace, with newly recognized diseases and their viral causes being reported, accompanied by ever more sophisticated techniques for studying these entities that exist at the fringes of the living world.
In this latest edition we have attempted to capture some of this dynamism, while retaining the organization and pedagogical approach of the original. To that end we have added new and expanded discussions of such agents as Ebola virus, Zika virus, and H1N1 and H7N9 influenza virus, as well as the SARS‐CoV‐2/COVID‐19 pandemic, with information that is current as of this writing. We have modified our presentation of techniques, removing some that are outdated (CoT curves, as an example), retaining the classics that have defined the field (pulse and pulse‐chase labeling), and introducing the newest approaches that are opening new areas of investigation (CRISPR‐Cas).
The organization of the book has been retained from the third edition, with 25 chapters divided into five parts, including the Case Studies, updated as necessary. We have tried to avoid textbook size creep by making judicious editorial choices. Figures have been changed as needed to reflect new information, with the addition of new graphics where necessary to complete new or expanded coverage.
We hope that you find this version of our work both useful and relevant in your teaching of our favorite topic . . . virology!
David Camerini, Martinez “Marty” Hewlett, and Dave Bloom: Michael's Kitchen and Bakery, Taos, New Mexico, March 2017.
Acknowledgments
Even the most basic text cannot be solely the work of its author or authors; this is especially true for this one. We are extremely grateful to a large number of colleagues, students, and friends. They provided critical reading, essential information, experimental data, and figures, as well as other important help for all four of the editions of Basic Virology. This group includes the following scholars from other research centers: Wah Chiu, Stanford University; J. Brown, University of Virginia; J. B. Flannegan and R. Condit, University of Florida; J. Conway, National Institutes of Health; K. Fish and J. Nelson, Oregon Health Sciences University; D. W. Gibson, Johns Hopkins University; P. Ghazal, University of Edinburgh; H. Granzow, Friedrich‐Loeffler‐Institut, Insel Riems; C. Grose, University of Iowa; J. Hill, Louisiana State University Eye Center–New Orleans; S. Karst, University of Florida; J. Langland, Arizona State University; D. Leib, Dartmouth College; F. Murphy, University of California, Davis; S. Rabkin, Harvard University; S. Rice, University of Alberta–Edmonton; S. Silverstein, Columbia University; B. Sugden, University of Wisconsin; Gail Wertz, University of Alabama–Birmingham; and J. G. Stevens, University of California, Los Angeles. Colleagues at the University of California, Irvine who provided aid include R. Davis, S. Larson, A. McPherson, T. Osborne, R. Sandri‐Goldin, D. Senear, B. Semler, S. Stewart, W. E. Robinson, I. Ruf, and L. Villarreal. Both current and former workers in Edward Wagner’s laboratory did many experiments that aided in a number of illustrations; these people include J. S. Aguilar, K. Anderson, R. Costa, G. B. Devi‐Rao, R. Frink, S. Goodart, J. Guzowski, L. E. Holland, P. Lieu, N. Pande, M. Petroski, M. Rice, J. Singh, J. Stringer, and Y.‐F. Zhang. Colleagues of David Camerini that did experiments and helped make figures used in the fourth edition are Joseph J. Campo, Shailesh K. Choudhary, Arlo Randall, and Robert M. Scoggins.
We were aided in the writing of the second edition by comments from Robert Nevins (Milsap College), Sofie Foley (Napier University), David Glick (King’s College), and David Fulford (Edinboro University of Pennsylvania).
We want to remember the many people who contributed to the physical process of putting the first edition of this book together. R. Spaete of the Aviron Corp carefully read every page of the manuscript and suggested many important minor and a couple of major changes. This was done purely in the spirit of friendship and collegiality. K. Christensen used her considerable expertise and incredible skill in working with us to generate the art. Not only did she do the drawings, but also she researched many of them to help provide missing details. Two undergraduates were invaluable to us. A. Azarian at University of California, Irvine made many useful suggestions on reading the manuscript from a student’s perspective, and D. Natan, an MIT student who spent a summer in Edward Wagner’s laboratory, did most of the Internet site searching, which was a great relief and time saver. Finally, J. Wagner carried out the very difficult task of copyediting the manuscript.
From the beginning, a number of people at Blackwell Science represented by Publisher N. Hill‐Whilton demonstrated a commitment to a quality product. We especially thank Nathan Brown, Cee Brandson, and Rosie Hayden, who made great efforts to maintain effective communications and to expedite many of the very tedious aspects of this project. Blackwell Science directly contacted a number of virologists who also read and suggested useful modifications to this manuscript: Michael R. Roner, University of Texas, Arlington; Lloyd Turtinen, University of Wisconsin, Eau Claire; and Paul Wanda, Southern Illinois University.
All of these colleagues and friends represent the background of assistance we have received, leading to the preparation of this fourth edition. We would especially like to acknowledge Dr. Luis Villarreal and the Center for Virus Research at the University of California, Irvine for supporting our efforts in bringing this book to a timely completion.
PART IVirology and Viral Disease
Introduction – The Impact of Viruses on Our View of Life
The Science of Virology
An Outline of Virus Replication and Viral Pathogenesis
Virus Replication
Pathogenesis of Viral Infection
Virus Disease in Populations and Individual Animals
The Nature of Virus Reservoirs
Viruses in Populations
Animal Models to Study Viral Pathogenesis
Patterns of Some Viral Diseases of Humans
The Dynamics of HUMAN–VIRUS Interactions
Patterns of Specific Viral Diseases of Humans
Some Viral Infections Targeting Specific Organ Systems
Problems for Part I
Additional Reading for Part I
CHAPTER 1Introduction – The Impact of Viruses on Our View of Life
THE SCIENCE OF VIROLOGY
The effect of virus infections on the host organism and populations – viral pathogenesis, virulence, and epidemiology
The interaction between viruses and their hosts
The history of virology
Examples of the impact of viral disease on human history
Examples of the evolutionary impact of the virus–host interaction
The origin of viruses
Viruses have a constructive as well as destructive impact on society
Viruses are not the smallest self‐replicating pathogens
QUESTIONS FOR CHAPTER 1
THE SCIENCE OF VIROLOGY
The study of viruses has historically provided and continues to provide the basis for much of our most fundamental understanding of modern biology, genetics, and medicine. Virology has had an impact on the study of biological macromolecules, processes of cellular gene expression, mechanisms for generating genetic diversity, processes involved in the control of cell growth and development, aspects of molecular evolution, the mechanism of disease and response of the host to it, and the spread of disease in populations.
In essence, viruses are collections of genetic information directed toward one end: their own replication. They are the ultimate and prototypical example of “selfish genes.” The viral genome contains the “blueprints” for virus replication enciphered in the genetic code, and must be decoded by the molecular machinery of the cell that it infects to gain this end. Viruses are thus obligate intracellular parasites dependent on the metabolic and genetic functions of living cells.
Given the essential simplicity of virus organization – a genome containing genes dedicated to self‐replication surrounded by a protective protein shell – it has been argued that viruses are nonliving collections of biochemicals whose functions are derivative and separable from the cell. Yet this generalization does not stand up to the increasingly detailed information accumulating describing the nature of viral genes, the role of viral infections in evolutionary change, and the evolution of cellular function. A view of viruses as constituting a major subdivision of the biosphere, as ancient as and fully interactive and integrated with the three great branches of cellular life, becomes more strongly established with each investigational advance.
It is a major problem in the study of biology at a detailed molecular and functional level that almost no generalization is sacred, and the concept of viruses as simple parasitic collections of genes functioning to replicate themselves at the expense of the cell they attack does not hold up. Many generalizations will be made in the survey of the world of viruses introduced in this book; most if not all will be ultimately classified as being useful, but unreliable, tools for the full understanding and organization of information.
Even the size range of viral genomes, generalized to range from one or two genes to a few hundred at most (significantly less than those contained in the simplest free‐living cells), cannot be supported by a close analysis of data. While it is true that the vast majority of viruses studied range in size from smaller than the smallest organelle to just smaller than the simplest cells capable of energy metabolism and protein synthesis, the mycoplasma and simple unicellular algae, the recently discovered mimivirus (distantly related to poxviruses such as smallpox or variola) contains nearly 1000 genes and is significantly larger than the smallest cells. With such caveats in mind, it is still appropriate to note that despite their limited size, viruses have evolved and appropriated a means of propagation and replication that ensures their survival in free‐living organisms that are generally between 10 and 10 000 000 times their size and genetic complexity.
The effect of virus infections on the host organism and populations – viral pathogenesis, virulence, and epidemiology
Since a major motivating factor for the study of virology is that viruses cause disease of varying levels of severity in human populations and in the populations of plants and animals that support such populations, it is not particularly surprising that virus infections have historically been considered episodic interruptions of the wellbeing of a normally healthy host. This view was supported in some of the earliest studies on bacterial viruses, which were seen to cause the destruction of the host cell and general disruption of healthy, growing populations of the host bacteria. Despite this, it was seen with another type of bacterial virus that a persistent, lysogenic infection could ensue in the host population. In this case, stress to the lysogenic bacteria could release infectious virus long after the establishment of the initial infection.
These two modes of infection of host populations by viruses, which can be accurately modeled by mathematical methods developed for studying predator–prey relationships in animal and plant populations, are now understood to be general for virus–host interactions. Indeed, persistent infections with low or no levels of viral disease are universal in virus–host ecosystems that have evolved together for extended periods – it is only upon the introduction of a virus into a novel population that widespread disease and host morbidity occur.
While we can therefore consider severe virus‐induced disease to be evidence of a recent introduction of the virus into the population in question, the accommodation of the one to the other is a very slow process requiring genetic changes in both virus and host, and it is by no means certain that the accommodation can occur without severe disruption of the host population – even its extinction. For this reason, the study of the replication and propagation of a given virus in a population is of critical importance to the body politic, especially in terms of formulating and implementing health policy. This is, of course, in addition to its importance to the scientific and medical communities.
The study of viral pathogenesis is broadly defined as the study of effects of viral infection on the host. The pathogenicity of a virus is defined as the sum total of the virus‐encoded functions that contribute to virus propagation in the infected cell, in the host organism, and in the population. Pathogenicity is essentially the genetic ability of members of a given specific virus population (which can be considered to be genetically more or less equivalent) to cause a disease and spread through (propagate in) a population. Thus, a major factor in the pathogenicity of a given virus is its genetic makeup or genotype.
The basis for severity of the symptoms of a viral disease in an organism or a population is complex. It results from an intricate combination of expression of the viral genes controlling pathogenicity, physiological response of the infected individual to these pathogenic determinants, and response of the population to the presence of the virus propagating in it. Taken together, these factors determine or define the virulence of the virus and the disease it causes.
A basic factor contributing to virulence is the interaction among specific viral genes and the genetically encoded defenses of the infected individual. It is important to understand, however, that virulence is also affected by the general health and genetic makeup of the infected population, and in humans, by the societal and economic factors that affect the nature and extent of the response to the infection.
The distinction and gradation of meanings between the terms pathogenesis and virulence can be understood by considering the manifold factors involved in disease severity and spread exhibited in a human population subjected to infection with a disease‐causing virus. Consider a virus whose genotype makes it highly efficient in causing a disease, the signs and symptoms of which are important in the spread between individuals – perhaps a respiratory infection with accompanying sneezing, coughing, and so on. This ideal or optimal virus will incorporate numerous, random genetic changes during its replication cycles as it spreads in an individual and in the population. Some viruses generated during the course of a disease may, then, contain genes that are not optimally efficient in causing symptoms. Such a virus is of reduced virulence, and in the extreme case, it might be a virus that has accumulated so many mutations in pathogenic genes that it can cause no disease at all (i.e., has mutated to an avirulent or apathogenic strain). While an avirulent virus may not cause a disease, its infection may well lead to complete or partial immunity against the most virulent genotypes in an infected individual. This is the basis of vaccination, which is described in Part II, Chapter 8. But the capacity to generate an immune response and the resulting generation of herd immunity also mean that as a virus infection proceeds in a population, either its virulence must change or the virus must genetically adapt to the changing host.
Other factors not fully correlated with the genetic makeup of a virus also contribute to variations in virulence of a pathogenic genotype. The same virus genotype infecting two immunologically naive
