Human
Virology

A text for students of medicine,
dentistry, and microbiology
Third edition

xvii
PART 1 General principles 1
1 Virology: how it all began 3
1 Introduction 3
2 How viruses were discovered 4
3 How they were grown in the laboratory 4
4 Sizes and shapes 4
5 Replication 5
6 The control of viral diseases 5
7 Conclusions 5
2 General properties of viruses 7
1 Introduction 7
2 The architecture of viruses 8
3 Classification of viruses 14
4 The nomenclature of viruses 15
5 The range of diseases caused by viruses 15
6 Reminders 16
3 Viral replication and genetics 19
1 Introduction 19
2 The molecular biology of the mammalian cell 19
3 Virus infection and replication in a host cell 20
4 Virus assembly, release from the host cell, and maturation 26
5 Genetic variation of viruses 27
6 Reminders 27
4 How viruses cause disease 29
1 Introduction 29
2 Viral factors: pathogenicity and virulence 29
3 Interactions between viruses and host cells 30
4 The spread of viruses in the host 31
5 Patterns of disease 37
6 Shedding of virus from the host 38
Contents
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x84 CoSnptecnitfisc infections
7 How infectious is a virus? 38
8 Reminders 38
5 Resistance to virus infections 39
1 Introduction: innate and adaptive immunity 39
2 General factors in resistance 40
3 Local non-specific defences 41
4 The adaptive immune system 43
5 T cells and cell-mediated immunity 46
6 Harmful immune responses 48
7 Resistance and recovery 49
8 Reminders 49
6 Viruses and cancer in humans 51
1 Historical note 51
2 General features of viral oncogenesis 53
3 Viral oncogenes 54
4 Cellular oncogenes 55
5 Indirect mechanisms 56
6 Viruses implicated in cancers of humans 56
7 Reminders 57
7 Viruses and the community 59
1 Introduction 59
2 Definitions 59
3 What use is epidemiology? 60
4 Epidemiological methods 60
5 Serological epidemiology 61
6 Factors in the spread of viral infections 62
7 Herd immunity 63
8 Hospital-acquired infections (HAIs) 65
9 The periodicity of epidemics 66
10 Control measures 67
11 Reminders 68
PART 2 Special infections 69
8 Upper respiratory tract and eye infections due to adenoviruses, coronaviruses
(including SARS CoV), and rhinoviruses 71
1 Introduction 71
2 Adenoviruses 71
3 Coronaviruses 73
4 Severe acute respiratory syndrome (SARS) 75
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5 Rhinoviruses 76
6 Reminders 77
9 Childhood infections caused by paramyxoviruses 79
1 Introduction 79
2 Properties of the Paramyxoviridae 79
3 Clinical and pathological aspects of paramyxovirus infections 81
4 Reminders 85
10 Orthomyxoviruses and influenza 87
1 Introduction 87
2 Properties of the orthomyxoviruses 87
3 Clinical and pathological aspects 92
4 Prevention and cure 93
5 Reminders 94
11 Gastroenteritis viruses 97
1 Introduction 97
2 Rotaviruses 97
3 Adenoviruses 100
4 Caliciviruses 100
5 Astroviruses 101
6 Laboratory diagnosis 101
7 Reminders 102
12 Rubella: postnatal infections 103
1 Introduction 103
2 Properties of the virus 103
3 Clinical and pathological aspects 103
4 Reminders 106
13 Parvoviruses 107
1 Introduction 107
2 Properties of the viruses 107
3 Clinical and pathological aspects 108
4 Reminders 109
14 Poxviruses 111
1 Introduction 111
2 Properties of the viruses 111
3 Clinical and pathological aspects of smallpox 113
4 Other poxvirus infections 117
5 Reminders 118
Contents xi
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15 Papovaviruses 119
1 Introduction 119
2 Properties of the viruses 119
3 Clinical and pathological aspects of papillomavirus infections 121
4 Clinical and pathological aspects of polyomavirus infections 124
5 Reminders 126
16 Poliomyelitis and other picornavirus infections 127
1 Properties of the viruses 127
2 Clinical and pathological aspects 129
3 Control measures 136
4 Reminders 136
17 The herpesviruses: general properties 137
1 Classification 137
2 Morphology 137
3 Genome 138
4 Polypeptides 138
5 Antigens 138
6 Replication 139
7 Reminders 139
18 The alphaherpesviruses: herpes simplex and varicella-zoster 141
1 Herpes simplex viruses 141
2 Varicella-zoster virus 146
3 Herpesvirus B 147
4 Reminders 148
19 The betaherpesviruses: cytomegalovirus and human herpesviruses 6 and 7 149
1 Cytomegalovirus 149
2 Human herpesviruses types 6 and 7 151
3 Reminders 152
20 The gammaherpesviruses: Epstein–Barr virus and Kaposi’s
sarcoma-associated herpesvirus 153
1 Epstein–Barr virus 153
2 Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) 156
3 Reminders 156
21 Introduction to the hepatitis viruses 159
1 Hepatitis A 160
2 Hepatitis B and deltavirus 160
3 Hepatitis C 160
4 Other hepatitis viruses 160
xii Contents
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22 The blood-borne hepatitis viruses B and delta 161
1 Properties of hepatitis B virus 161
2 Clinical and pathological aspects of hepatitis B virus infections 163
3 Properties of delta virus 169
4 Clinical and pathological aspects of hepatitis delta virus infections 170
5 Reminders 170
23 The enteric hepatitis viruses A and E 171
1 Properties of hepatitis A virus 171
2 Clinical and pathological aspects of hepatitis A virus infections 172
3 Reminders 173
4 Properties of hepatitis E virus 173
5 Clinical and pathological aspects of hepatitis E virus infections 173
6 Reminders 173
24 The blood-borne hepatitis flaviviruses 175
1 Properties of hepatitis C virus 175
2 Clinical and pathological aspects of hepatitis C virus infections 176
3 The GBV viruses 177
4 Reminders 178
25 Retroviruses and AIDS 179
1 Introduction 179
2 Properties of HIV 180
3 Clinical and pathological aspects of HIV 183
4 The discovery of the other human retroviruses: HTLV-I and HTLV-II 187
5 Reminders 188
26 Lyssavirus and rabies 189
1 Introduction 189
2 Properties of the virus 189
3 Clinical and pathological aspects 190
4 Reminders 194
27 Arthropod-borne viruses 195
1 Introduction 195
2 Properties of the viruses 196
3 Clinical and pathological aspects of arbovirus infections 197
4 Reminders 203
28 Exotic and dangerous infections: filoviruses, arenaviruses, and hantaviruses 205
1 Introduction 205
2 Filoviruses 206
3 Arenaviruses 208
4 Hantaviruses 211
Contents xiii
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5 Risk categories 213
6 Reminders 213
29 Prions and the spongiform encephalopathies 215
1 Prion diseases 215
2 What are prions? 217
3 Pathogenesis and pathology 218
4 Laboratory diagnosis 218
5 Safety measures 218
6 The great bovine spongiform encephalopathy outbreak 219
7 Reminders 220
PART 3 Special syndromes 221
30 Viral diseases of the central nervous system 223
1 Acute infections (Group 1) 224
2 Acute postexposure syndromes (Group 2) 226
3 Chronic infections (Group 3) 227
4 Laboratory diagnosis 227
5 Reminders 228
31 Intrauterine and perinatal infections 229
1 Pathogenesis 229
2 Fetal immunity 230
3 Specific infections 231
4 Reminders 237
32 Viral infections in patients with defective immunity 239
1 Introduction 239
2 Primary immunodeficiencies 239
3 Acquired immunodeficiencies secondary to other diseases and their treatment 241
4 Some special problems 241
5 Diagnosis and treatment 244
6 Reminders 244
33 Respiratory infections 247
34 Sexually transmitted viral infections 249
35 Resurgent and emergent viral infections 253
1 Introduction 253
2 Factors favouring the resurgence of old enemies 254
3 The emergence of new enemies 255
4 Reminders 256
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PART 4 Practical aspects 257
36 The laboratory diagnosis of viral infections 259
1 Introduction 259
2 Collecting and sending clinical specimens to the laboratory 260
3 Rapid diagnostic methods 260
4 Virus isolation in cell cultures 264
5 Detection of antiviral antibodies 266
6 Reminders 267
37 Control of viral diseases by immunization 269
1 The technology and practicalities of virus vaccine production and development 269
2 Virus vaccines and public health 272
3 Passive immunization 274
4 New approaches to vaccine development 274
5 Reminders 275
38 Antiviral chemotherapy 277
1 Points of action of antivirals in the virus life cycle 277
2 The use of antivirals: general considerations 278
3 Herpes infections 280
4 Influenza 281
5 HIV infections 281
6 Interferons 283
7 The future 283
8 Reminders 284
Appendices 285
A Safety precautions: codes of practice, disinfection, and sterilization 287
1 Introduction 287
2 The clinical phase 287
3 The laboratory phase 288
4 Further reading 289
B Viral infections notifiable in the UK 291
C Suggestions for further reading 293
General virology 293
Immunology 293
Index 295
Contents xv

Although not many would agree entirely with the great industrialist’s
dismissal of the past, there is certainly a tendency for
today’s students of science to regard the history of their subjects
as a waste of time. Given the sheer volume of material that has
to be absorbed, digested, and regurgitated in the examinations,
this feeling is understandable; but it is a pity, because history,
especially that of virology, provides not only a fascinating
account of technological developments in microbiology, but
also the intellectual challenge of thinking about how life
began.
Viruses do not leave fossils, and our views on their origin
must be based on the most slender of clues; the rest is at present
speculation, based mostly on our knowledge of the behaviour of
today’s viruses, bacteria, and cells, but influenced sometimes by
individual ideas of religion and even cosmology. For example,
some believe that viruses, like all other life forms, were divinely
created, and others that they originated in comets or elsewhere
in outer space. However, most people would probably take the
intuitive approach that simple organisms preceded more complicated
ones, and that bacteria evolved from what were once
free-living, self-replicating molecules that resemble today’s
viruses. However, this superficially attractive argument ignores
the fact that modern viruses have an absolute requirement for
living cells in which to multiply, and that—as far as we know—
no such organic, self-replicating molecules exist nowadays.
An alternative notion is that viruses evolved from cellular
components—nucleic acids and proteins—as semi-independent
agents able to replicate only by exploiting the energy
and reproductive machinery of the cells of higher organisms