Introduction to Modern Virology

Nigel Dimmock is an internationally acclaimed virologist who has spent the major part of his career at the University of Warwick where he is an emeritus Professor. His main research interests are influenza virus and antiviral strategies. Andrew Easton is a Professor of Virology at the University of Warwick. His research focuses on the molecular biology and pathogenesis of respiratory viruses, particularly respiratory syncytial virus and influenza virus and the control of translation of virus mRNA. Keith Leppard is an Associate Professor (Reader) at the University of Warwick. His research focuses on adenoviruses: their replication, the effects of viral proteins on the host cell, and on the development of the virus as a gene delivery vehicle.

• Preface xviiAbout the companion website xixPart I The Nature of Viruses 1Chapter 1 Towards a definition of a virus 31.1 Discovery of viruses 41.2 Multiplication of viruses 51.3 The virus multiplication cycle 61.4 Viruses can be defined in chemical terms 71.5 Multiplication of bacterial and animal viruses is fundamentally similar 101.6 Viruses can be manipulated genetically 111.7 Properties of viruses 111.8 Origin of viruses 12Key points 12Further reading 12Chapter 2 The structure of virus particles 132.1 Virus particles are constructed from subunits 132.2 The structure of filamentous viruses and nucleoproteins 142.3 The structure is of isometric virus particles 152.4 Enveloped (membrane-bound) virus particles 242.5 Virus particles with head-tail morphology 272.6 Frequency of occurrence of different virus particle morphologies 282.7 Principles of disassemply: virus particles are metastable 28Key points 29Further reading 29Chapter 3 Classification of viruses 303.1 Classification on the basis of disease 303.2 Classification on the basis of host organism 313.3 Classification on the basis of virus particle morphology 313.4 Classification on the basis of viral nucleic acids 323.5 Classification on the basis of taxonomy 343.6 Satellites, viroids and prions 35Key points 37Further reading 38Chapter 4 The evolution of viruses 394.1 Mechanisms of virus evolution 404.2 The potential for rapid evolution: mutation and quasispecies 404.3 Rapid evolution: recombination 434.4 Rapid evolution: reassortment 434.5 Evolution to find a host, and subsequent co-evolution with the host 46Key points 51Questions 51Further reading 51Chapter 5 Techniques for studying viruses 525.1 Culturing wild virus isolates 525.2 Enumeration of viruses 545.3 Measuring infectious virus titres 555.4 Measuring physical virus titres 575.5 Detecting virus in a sample 585.6 Understanding virus replication cycles 625.7 Viral genetics and reverse genetics 635.8 Systems-level virology 63Key points 65Questions 65Further reading 65Part II Virus Growth in Cells 67Chapter 6 The process of infection: I. Virus attachment and entry into cells 696.1 Infection of animal cells: the nature and importance of receptors 696.2 Infection of animal cells: enveloped viruses 736.3 Infection of animal cells: non-enveloped viruses 786.4 Infection of plant cells 806.5 Infection of bacteria 816.6 Infection of cells: post-entry events 826.7 Virus entry: cell culture and the whole organism 84Key points 84Questions 84Further reading 85Chapter 7 The process of infection: IIA. The replication of viral DNA 867.1 The universal mechanism of DNA synthesis 877.2 Replication of circular double-stranded DNA genomes 907.3 Replication of linear double-stranded DNA genomes that can form circles 937.4 Replication of linear double-stranded DNA genomes that do not circularize 967.5 Replication of single-stranded circular DNA genomes 1007.6 Replication of single-stranded linear DNA genomes 1007.7 Dependency versus autonomy among DNA viruses 103Key points 103Questions 103Further reading 103Chapter 8 The process of infection: IIB. Genome replication in RNA viruses 1058.1 Nature and diversity of RNA virus genomes 1068.2 Regulatory elements for RNA virus genome synthesis 1068.3 Synthesis of the RNA genome of Baltimore class 3 viruses 1118.4 Synthesis of the RNA genome of Baltimore class 4 viruses 1118.5 Synthesis of the RNA genome of Baltimore class 5 viruses 1158.6 Synthesis of the RNA genome of viroids and hepatitis delta virus 118Key points 119Questions 119Further reading 119Chapter 9 The process of infection: IIC. The replication of RNA viruses with a DNA intermediate and vice versa 1219.1 The retrovirus replication cycle 1229.2 Discovery of reverse transcription 1229.3 Retroviral reverse transcriptase 1239.4 Mechanism of retroviral reverse transcription 1259.5 Integration of retroviral DNA into cell DNA 1289.6 Production of retrovirus progeny genomes 1309.7 Spumaviruses: retrovirus with unusual features 1319.8 The hepadnavirus replication cycle 1319.9 Mechanism of hepadnavirus reverse transcription 1319.10 Comparing reverse transcribing viruses 134Key points 134Questions 134Further reading 135Chapter 10 The process of infection: IIIA. Gene expression in DNA viruses and reverse-transcribing viruses 13610.1 The DNA viruses and retroviruses: Baltimore classes 1, 2, 6 and 7 13710.2 Polyomaviruses 13810.3 Papillomaviruses 14210.4 Adenoviruses 14410.5 Herpesviruses 14710.6 Poxviruses 14910.7 Parvoviruses 14910.8 Retroviruses 15010.9 Hepadnaviruses 15310.10 DNA bacteriophages 154Key points 154Questions 155Further reading 155Chapter 11 The process of infection: IIIB. Gene expression and its regulation in RNA viruses 15611.1 The RNA viruses: Baltimore classes 3, 4 and 5 15711.2 Reoviruses 15811.3 Picornaviruses 16311.4 Alphaviruses 16411.5 Coronaviruses 16611.6 Negative sense RNA viruses with segmented genomes 16911.7 Orthomyxoviruses 16911.8 Arenaviruses 17311.9 Negative sense RNA viruses with non-segmented, single stranded genomes: rhabdoviruses and paramyxoviruses 174Key points 177Questions 178Further reading 178Chapter 12 The process of infection: IV. The assembly of viruses 17912.1 Self-assembly from mature virion components 18012.2 Assembly of viruses with a helical structure 18012.3 Assembly of viruses with an isometric structure 18412.4 Assembly of complex viruses 18712.5 Sequence-dependent and -independent packaging of virus DNA in virus particles 18912.6 The assembly of enveloped viruses 19012.7 Segmented virus genomes: the acquisition of multiple nucleic acid molecules 19412.8 Maturation of virus particles 195Key points 196Questions 197Further reading 197Part III Virus Interactions with the Whole Organism 199Chapter 13 Innate and intrinsic immunity 20113.1 Innate immune responses in vertebrates – discovery of interferon 20213.2 Induction of type 1 interferon responses 20313.3 Virus countermeasures to innate immunity 20713.4 TRIM proteins and immunity 20913.5 Intrinsic resistance to viruses in vertebrates 21013.6 Innate and intrinsic immunity and the outcome of infection 21213.7 RNAi is an important antiviral mechanism in invertebrates and plants 21213.8 Detecting and signalling infection in invertebrates and plants 21413.9 Virus resistance mechanisms in bacteria and archaea 215Key points 216Questions 217References 217Chapter 14 The adaptive immune response 21814.1 General features of the adaptive immune system 21914.2 Cell-mediated immunity 22114.3 Antibody-mediated humoral immunity 22614.4 Virus evasion of adaptive immunity 23214.5 Age and adaptive immunity 23314.6 Interaction between the innate and adaptive immune systems 233Key points 234Questions 236Further reading 236Chapter 15 Interactions between animal viruses and cells 23715.1 Acutely cytopathogenic infections 23815.2 Persistent infections 23815.3 Latent infections 24115.4 Transforming infections 24315.5 Abortive infections 24315.6 Null infections 24415.7 How do animal viruses kill cells? 244Key points 246Questions 247Further reading 247Chapter 16 Animal virus–host interactions 24816.1 Cause and effect: Koch’s postulates 24816.2 A classification of virus–host interactions 24916.3 Acute infections 25216.4 Subclinical infections 25316.5 Persistent and chronic infections 25416.6 Latent infections 25616.7 Slowly progressive diseases 25716.8 Virus-induced tumours 258Key points 259Questions 260Further reading 260Chapter 17 Mechanisms in virus latency 26117.1 The latent interaction of virus and host 26117.2 Gene expression and the lytic and lysogenic life of bacteriophage λ 26317.3 Herpes simplex virus latency 27017.4 Epstein-Barr virus latency 27417.5 Latency in other herpesviruses 27517.6 HIV-1 latency 277Key points 277Questions 278Further reading 278Chapter 18 Transmission of viruses 27918.1 Virus transmission cycles 27918.2 Barriers to transmission 28118.3 Routes of horizontal transmission in animals 28218.4 Vertical transmission 28518.5 Vector-borne viruses and zoonotic transmission 28718.6 Epidemiology of virus infections 28918.7 Sustaining infection in populations 290Key points 291Questions 291Further reading 291Part IV Viruses and Human Disease 293Chapter 19 Human viral disease: an overview 29519.1 A survey of human viral pathogens 29519.2 Factors affecting the relative incidence of viral disease 29719.3 Factors determining the nature and severity of viral disease 29919.4 Common signs and symptoms of viral infection 30119.5 Acute viral infection 1: gastrointestinal infections 30219.6 Acute viral infection 2: respiratory infections 30419.7 Acute viral infection 3: systemic spread 30619.8 Acute viral disease: conclusions 306Key points 307Questions 308Further reading 308Chapter 20 Influenza virus infection 30920.1 The origins of human influenza viruses 30920.2 Influenza virus replication 31520.3 Influenza virus infection and disease 31620.4 Virus determinants of disease 32120.5 Host factors in influenza virus disease 32220.6 The immune response and influenza virus 32320.7 Anti-influenza treatment 324Key points 325Questions 326Further reading 326Chapter 21 HIV and AIDS 32721.1 Origins and spread of the HIV pandemic 32721.2 Molecular biology of HIV 33021.3 HIV transmission and tropism 33821.4 Course of HIV infection: pathogenesis and disease 33921.5 Immunological abnormalities during HIV infection 34221.6 Prevention and control of HIV infection 343Key points 345Questions 346Further reading 346Chapter 22 Viral hepatitis 34722.1 The signs and symptoms of hepatitis 34722.2 Hepatitis A virus infections 34922.3 Hepatitis E virus infections 35022.4 Hepatitis B virus infections 35222.5 Hepatitis D virus infections 35522.6 Hepatitis C virus infections 356Key points 359Questions 361Further reading 361Chapter 23 Vector-borne infections 36223.1 Arboviruses and their hosts 36223.2 Yellow fever virus 36323.3 Dengue virus 36723.4 Chikungunya virus 36923.5 West Nile virus in the USA 372Key points 375Questions 375Further reading 375Chapter 24 Exotic and emerging viral infections 37624.1 Ebola and Marburg viruses: emerging filoviruses 37724.2 Hendra and Nipah viruses: emerging paramyxoviruses 38124.3 SARS and MERS: emerging coronaviruses 38324.4 Predicting the future: clues from analysis of the genomes of previously unknown viruses 386Key points 386Questions 386Further reading 387Chapter 25 Carcinogenesis and tumour viruses 38825.1 Immortalization, transformation and tumourigenesis 38925.2 Oncogenic viruses 39025.3 Polyomaviruses, papillomaviruses and adenoviruses: the small DNA tumour viruses as experimental models 39425.4 Papillomaviruses and human cancer 39825.5 Polyomaviruses and human cancer 39925.6 Herpesvirus involvement in human cancers 40025.7 Retroviruses as experimental model tumour viruses 40225.8 Retroviruses and naturally-occurring tumours 40425.9 Hepatitis viruses and liver cancer 40525.10 Prospects for the control of virus-associated cancers 406Key points 407Questions 408Further reading 408Chapter 26 Vaccines and immunotherapy: the prevention of virus diseases 40926.1 The principles of vaccination 41126.2 Whole virus vaccines 41226.3 Advantages, disadvantages and difficulties associated with whole virus vaccines 41526.4 Subunit vaccines 42026.5 Advantages, disadvantages and difficulties associated with subunit vaccines 42126.6 Considerations for the generation and use of vaccines 42226.7 Adverse reactions and clinical complications with vaccines 42326.8 Eradication of virus diseases by vaccination 42526.9 Immunotherapy for virus infections 42826.10 Adverse reactions and clinical complications with immunotherapy 429Key points 429Questions 430Further reading 430Chapter 27 Antiviral therapy 43127.1 Scope and limitations of antiviral therapy 43127.2 Antiviral therapy for herpesvirus infections 43227.3 Antiviral therapy for influenza virus infections 43427.4 Antiviral therapy for HIV infections 43527.5 Antiviral therapy for hepatitis virus infections 43927.6 Therapy for other virus infections 440Key Points 441Questions 441Further Reading 442Chapter 28 Prion diseases 44328.1 The spectrum of prion diseases 44328.2 The prion hypothesis 44428.3 The aetiology of prion diseases 44728.4 Prion disease pathogenesis 44828.5 Bovine spongiform encephalopathy (BSE) 45128.6 BSE and the emergence of variant CJD 45328.7 Concerns about variant CJD in the future 45428.8 Unresolved issues 455Key points 456Questions 456Further reading 456Part V Virology – The Wider Context 459Chapter 29 The economic impact of viruses 46129.1 The economics of virus infections of humans 46229.2 The economics of virus infections of animals 46429.3 The economics of virus infections of plants 46629.4 The Netherlands tulip market crash 469Key points 470Further reading 470Chapter 30 Recombinant viruses: making viruses work for us 47230.1 Recombinant viruses as vaccines 47330.2 Recombinant viruses for gene therapy 47430.3 Retroviral vectors for gene therapy 47630.4 Adenovirus vectors for gene therapy 47830.5 Parvovirus vectors for gene therapy 48030.6 Oncolytic viruses for cancer therapy 48030.7 Recombinant viruses in the laboratory 482Key points 482Questions 482Further reading 483Chapter 31 Viruses: shaping the planet 48431.1 Virus infections can give a host an evolutionary advantage 48431.2 Endogenous retroviruses and host biology 48531.3 Bacteriophage can be pathogenicity determinants for their hosts 48831.4 Cyanophage impacts on carbon fixation and oceanic ecosystems 48831.5 Virology and society: for good or ill 489Key points 490Questions 490Further reading 490Index 491