Respiratory Syncytial Virus (eBook)

Cover 1
Respiratory Syncytial Virus 4
Copyright Page 5
Contents 6
Preface 8
Molecular Biology of Human Respiratory Syncytial Virus 10
Introduction 10
The virion 11
The infectious cycle 12
Experimental systems to study the replicative cycle of HRSV 12
Virus entry 15
Transcription and replication of the viral genome 26
Virus assembly 36
Virus-host cell interactions 37
Acknowledgements 39
References 39
Immunology of RSV 52
The innate immune response 52
The adaptive immune response 58
Conclusions 78
References 79
Molecular Epidemiology and Evolution of RSV 98
Introduction 98
RSV groups and genotypes 98
Structure of epidemics 99
Geographic distribution of RSV strains 103
The G protein 104
Evolution of RSV 104
Emergence of new lineages 107
Disappearance of lineages 110
Mechanism of selection of new strains 110
Paradox 112
Reinfection with RSV 113
Conclusions 114
References 114
Genetic Susceptibility to RSV Disease 124
Epidemiological evidence of genetic susceptibility to RSV infection in infancy 125
Evidence that the host response rather than the virus is responsible for disease 128
Requirements for effective genetic association studies 129
Genetic association studies of RSV bronchiolitis 136
Other studies 143
General comments 143
The future 143
References 144
Pathogenesis of RSV in Children 150
Introduction 150
Viral infection and cytotoxicity 150
The immune response to infection 151
Conclusion 163
References 163
RSV Infection in Elderly Adults 172
Introduction 172
Epidemiology 172
Clinical manifestations and complications of RSV infection in elderly adults 178
Diagnosis of RSV infection 179
Treatment of RSV infection 183
Prevention of RSV infection 184
Conclusions 185
References 185
Respiratory Syncytial Virus Disease Burden in the Developing World 192
Introduction 192
Methods, definitions, limitations 193
Denominator-based data on incidence 193
Associated mortality 210
Disease-causing agent or benign co-infection 214
Risk factors for RSV infection 221
Additional burdens of disease 223
Temporal dynamics of RSV: Where and how does it persist 224
Conclusions and future research needs 228
Abbreviations 232
References 233
Vaccines against Human Respiratory Syncytial Virus 242
Introduction: the burden of disease and the need for a vaccine 242
Considerations in developing an RSV vaccine 244
Formalin-inactivated RSV (FI-RSV) 249
Subunit vaccines 250
Live-attenuated RSV strains 255
Live-vectored RSV vaccines 267
DNA vaccines 271
Perspective 272
Acknowledgment 273
References 273
Development of Antivirals against Respiratory Syncytial Virus 288
Introduction 288
Slow progress 288
Vaccines versus antivirals 289
Brief history of RSV antiviral development 290
Modern approaches to antiviral discovery 291
Models of RSV disease 291
Alternative model of human RSV in tissue culture 295
Clinical trials of RSV agents 295
Drugs in development 296
Miscellaneous (unknown) mechanisms 300
Inhibiting host cell functions 300
Antisense compounds and siRNA 300
Future prospects 302
Acknowledgements 302
References 302
Pneumonia Virus of Mice 308
The natural history of PVM 308
Characteristics of the PVM virion 309
The molecular biology of PVM 310
PVM proteins 312
Pathogenesis of PVM infection in inbred strains of mice: basic biology 315
Explorations with the PVM infection model: therapeutic directions 318
References 322
Colour Section 330
List of Contributors 340
Index 344