Flaviviruses: Pathogenesis and Immunity (eBook)

Cover 1
Contents 6
Chapter 1. Molecular Determinants of Virulence: The Structural and Functional Basis for Flavivirus Attenuation 16
I. Introduction. 16
II. Morphology and Genome Structure. 17
III. Molecular Determinants of Virulence 18
IV. Conclusion 45
References 47
Chapter 2. Genetic Resistance to Flaviviruses 58
I. Introduction 59
II. Initial Discoveries of Genetic Resistance to Flaviviruses in Mice 60
III. Flavivirus Genetic Resistance in Wild Mice 63
IV. Development of Congenic Flavivirus-Resistant and -Susceptible Mouse Strains 65
V. Virus Specificity of the Flvr Phenotype in Mice 66
VI. Characteristics of the Flvr Phenotype 67
VII. Other Characteristics of Resistant C3H.PRI-Flvr Mice 79
VIII. Mapping the Flv Gene to Chromosome 5 82
IX. Analysis of Other Known Genes that Map Close to the Flv Locus on Chromosome 5 83
X. Positional Cloning of the Flv Gene 84
XI. Identification of the Flv Gene as Oas1b 87
XII. Possible Mechanism of Action of the Resistant Allele of the Oas1b Gene 88
XIII. Conclusions 90
References 94
Chapter 3. Immunobiology of Mosquito-Borne Encephalitic Flaviviruses 102
I. Introduction 102
II. Innate Immune Responses 107
III. Adaptive Immune Response 110
IV. Virus-Host Interplay in Immunity and Pathogenesis 120
References 124
Chapter 4. Immune Modulation by Flaviviruses 136
I. Introduction 137
II. Strategies for Virus Survival in the Immune-Competent Host 138
III. Flavivirus Upregulates Cell Surface Recognition Molecules 142
IV. Mechanisms of Upregulation 148
V. Models of WNV Disease Pathogenesis 151
VI. The Paradox of Cell Surface Moldecule Upregulation, Immunopathology, and Virus Survival 158
VII. Flavivirus Modulation of Adaptive Immune Responses: A Hypothesis 160
VIII. Maternal Tolerance: A Model of Embryonic Implantation 162
IX. Conclusions 163
References 164
Chapter 5. Mechanisms of DengueVirus-Induced Cell Death 172
I. Introduction 173
II. Apoptosis and Necrosis 174
III. Molecular Machinery of Apoptosis 176
IV. Virus-Induced Apoptosis 185
V. Apoptotic Cell Death in Response to Dengue Virus Infection 186
VI. Concluding Remarks 194
References 196
Chapter 6. Dynamics Flavivirus Infection in Mosquitoes 202
I. Mosquito Vectors Associated with Flaviviruses 203
II. Flavivirus Infection of and Replication in the Mosquito Vector 206
III. Vectorial Capacity 208
IV. Impact of Reproductive Biology on Dynamics of Flavivirus Transmission 215
V. Role of the Vector in Perpetuation of Virus over Adverse Seasons and Years 219
VI. Genetics of Infection 222
VII. Vector Control 228
VIII. Future Directions 231
References. 231
Chapter 7. Dynamics of Infection in Tick Vectors and at the Tick-Host Interface 248
I. Introduction to Ticks 249
II. Tick-Borne Flaviviruses 251
III. Anatomy and Dynamics of Infection in Ticks 251
IV. Nonviremic Transmission 260
V. Population Biology of Tick-Borne Flaviviruses 264
VI. Tick-Borne Transmission on Immune Hosts 266
VII. Role of Skin in Tick-Borne Transmission 268
VIII. Saliva-Activated Transmission 272
IX. Host Modulation by Tick Saliva 274
X. The ‘‘Red Herring’’ Hypothesis 280
References 281
Chapter 8. Pathogenesis of Flavivirus Encephalitis 288
I. Introduction 288
II. Host Factors 289
III. Arthropod Factors Affecting Pathogenesis 292
IV. Extraneural Infection 293
V. Cellular Receptors for Flaviviruses 294
VI. Cellular Tropism of Encephalitic Flaviviruses 296
VII. Immune Responses to Flaviviruses and Their Roles in Pathogenesis 298
VIII. Neuroinvasion 309
IX. Neuropathology 311
X. The Central Nervous System Immune Response 318
XI. Neuropathogenesis: West Nile Virus as a Model 323
XII. Virus Persistence 327
References 331
Chapter 9. Pathogenesis and Pathophysiology of Yellow Fever 358
I. Introduction 358
II. Disease Syndrome 359
III. Virus-Specific Virulence Factors 362
IV. Virus–Cell Interactions 372
V. Infection of Organized Tissues 376
VI. Pathogenesis and Pathophysiology in the Intact Host 379
VII. Responses to Live Yellow Fever (YF) 17D Vaccine in Humans 395
VIII. Summary 399
References 399
Chapter 10. Immunology and Immunopathogenesis of Dengue Disease 412
I. Introduction 413
II. Characteristics of Dengue Viruses 413
III. Sequential Infections with Dengue Viruses 413
IV. Clinical/Epidemiological Observations 414
V. Cellular Immunology of Dengue Viruses 415
VI. Immunopathogenesis of DHF 421
VII. Needs for Future Research 429
References 429
Chapter 11. Neutralization and Antibody-Dependent Enhancement of DengueViruses 436
I. Introduction 437
II. Neutralization(NT) and Protection by Antibodies 437
III. Studies in Monkeys: Definition of the ‘‘Protected’’ Antibody Response 440
IV. Antibody-Dependent Enhancement: Clinical and Epidemiological Evidence of Immunologically Enhanced Disease 444
V. Viral Factors 458
VI. ADE in Vivo 461
VII. ADE in Vitro 464
VIII. Discussion 474
References. 475
Index 484
Color Plate Section 502