Foot and Mouth Disease: Current Perspectives

Foot and Mouth Disease Current Perspectives......Page 2
Contents......Page 5
Contributors......Page 8
Preface......Page 11
1. Introduction......Page 13
2.3. Demonstration of Antigenic Variation 1922-1954......Page 15
2.4. Development of a Vaccine Against FMD 1925-1948......Page 17
2.5. Attenuated Vaccines......Page 19
3.2. Characteristics of Virus Components 1955 - Present......Page 20
4. The Rocky Road Towards New Vaccines......Page 22
4.1. The Peptide Approach......Page 23
5. The Carrier Issue......Page 24
6. The Future......Page 25
References......Page 26
1. Introduction......Page 30
3.1. The S-Fragment......Page 33
3.2. The poly(C) Tract and Pseudoknots......Page 34
3.3. A Cis-acting Replication Element (ere)......Page 35
4. The IRES Element- Structure and Function......Page 36
4.1. Structural Motifs in the FMDV IRES Element and Their Role in Function......Page 37
4.2. Features of the RNA Structure That Mediate Interaction of Translation Initiation Factors with the FMDV IRES......Page 40
4.3. RNA-Binding Proteins and FMDV IRES Organization......Page 42
5.1. Selection of the Initiation Site for Protein Synthesis......Page 44
5.2. The Leader Protease......Page 46
5.4. The P2 Proteins......Page 48
5.5. The P3 Proteins......Page 49
5.7. The 3D RNA Polymerase......Page 50
6. Structure and Function of the FMDV 3\'UTR......Page 51
7.1. Interactions of Viral Proteins With Cellular Components......Page 52
9. Acknowledgements......Page 53
References......Page 54
1. Introductory Overview......Page 64
2. FMDV Polyprotein Processing......Page 66
3.1. The Catalytic Mechanism of 3cpro......Page 67
3.3. RNA Binding Properties of 3cpro......Page 69
4. The L Proteinase......Page 71
4.2. \'Leaderless\' FMDV......Page 72
5. The 2A Oligopeptide......Page 73
5.1. The \'Translational\' Model of 2A-Mediated Cleavage: Implications for TheBiology of FMDV......Page 74
5.2. \'2A-Like\' Sequences......Page 75
6. The Cleavage of Host-Cell Proteins......Page 76
References......Page 79
1. Introduction......Page 88
2. Structural Overview of Picornaviruses......Page 89
3. FMDVs Structures......Page 93
3.1.Conformation of the Structural Proteins......Page 94
3.2. Capsid Stability......Page 96
4. Cellular Receptors......Page 97
5. Conclusions......Page 100
References......Page 101
1. Introduction......Page 104
2. Cattle......Page 107
3. Pigs......Page 108
5. Other Species......Page 111
References......Page 112
1. Introduction......Page 114
2.1. Historical Perspective......Page 115
2.3. Carrier Prevalence Under Field Conditions......Page 116
3.3. Challenge Dose......Page 118
4. Duration of Persistence......Page 120
5. Evidence of Transmission of FMDV from Carrier Animals......Page 121
6. Diagnosis of Persistent FMDV Infection......Page 124
7. The Carrier Threat......Page 127
8.1.1. Induction ofan Ineffective Immune Response......Page 128
8.1.2. Replication in an Immunologically Privileged Site......Page 130
8.2. Interference with the Immune Response......Page 131
8.3.1. Antigenic Variation......Page 133
8.3.2. Viral Interference......Page 137
8.3.4. Attenuation of Virulence......Page 138
9. Conclusion......Page 143
References......Page 144
1. Introduction......Page 155
2.1. Identification of Integrins as Viral Receptors......Page 157
2.2. Mechanisms of FMDV Entry......Page 160
2.3. Alternative Receptors for FMDV......Page 162
2.4. Role of the Receptor in FMDV Pathogenesis......Page 164
3.1. Viral Proteases......Page 165
3.2. P3 Proteins......Page 167
3.3. Viral Genetic Elements......Page 168
References......Page 170
1. Induction of Immune Responses: The FMDV-Specific Immune Responses......Page 183
1.2. Antigen Processing/Presentation......Page 187
1.4. Stimulation of B Lymphocytes......Page 190
1.5. Memory......Page 191
1.6. Cytokines......Page 192
1.7. Conclusions......Page 194
2.2. Relative Importance of Monocytes and DC in Induction of Anti-FMDV Immune Responses......Page 195
2.3. Conclusions......Page 197
3.3. Neutralising Anti-FMDV Antibodies......Page 198
3.4. Antibody Isotypes and the Kinetics of Their Induction......Page 199
4.1. Identification of Th lymphocyte response against FMDV......Page 200
4.3. Epitopes Recognised by Th Lymphocytes......Page 202
4.5. Conclusions......Page 205
5.1. Overview of Innate Immune Defences......Page 206
5.2. The Role of Dendritic Cells......Page 208
5.3. The Role of the Phagocytes......Page 209
5.4. The Specific Effector Anti-FMDV Immune Response: The Role of Antibody......Page 211
6.1. Macrophages and the Phagocytosis of FMDV......Page 212
6.2. Macrophages and FMDV/Antibody Complexes......Page 213
6.3. The Protective Immune Response (In Vivo) Against FMDV......Page 216
7. Cytotoxic Effector Immune Responses......Page 218
8. Influence of FMDV on Immune Defence Compartments......Page 219
8.1. FMDV Interaction With Cells of the Innate Immune Defences......Page 220
8.2. FMDV Survival Within Cells of the Innate Immune Defences......Page 221
8.3. Consequences of FMDV Interaction With Cells of Innate Immune Defences......Page 223
9. Conclusions......Page 224
References......Page 225
1. Introduction......Page 233
3.1. Conceptual Distinctions......Page 235
3.1.2. Contact, Functional and Energetic Epitopes......Page 236
3.2. The Antigenic G-H Loop of VP1......Page 237
3.3.1. Serotype O......Page 238
3.3.2. Serotype A......Page 239
3.4. Immunodominance of Different Antigenic Sites in the Natural Hosts......Page 240
3.5. A Continuum of Discontinuous Epitopes?......Page 241
3.6. Conclusion: A Consensus Antigenic Structure for FMDV......Page 243
4.1. 1. Early Work......Page 244
4.1.2. Functional Features of Individual G-H Loop Epitopes......Page 245
4.1.4. Comparative Antigenic Specificities of MAbs and Polyclonal Antibody Populations from Animal Hosts......Page 246
4.2.2. Carrier Proteins and Virus Chimeras......Page 247
4.3. Spectroscopic Studies of G-H Loop Peptides......Page 248
4.4. Crystallographic Studies of G-H Loop Peptide-Antibody Complexes......Page 249
4.4.2. A Genera/ Conformation for the Free and Antibody-Comp/exed G-H Loop......Page 250
4.4.3. Induced-Fit Recognition Between Antibodies and G-H Loop Peptides......Page 251
4.5. Cryo-Electron Microscopy Studies of Virion-Antibody Complexes......Page 252
4.6. Conclusion: A Structural and Functional Model of the Antigenic G-H Loop of FMDV......Page 254
5. Peptide Mimics of Discontinuous FMDV Epitopes......Page 255
6. Neutralization of FMDV Infectivity by Antibodies......Page 256
7.1. Extreme Antigenic Variation in FMDV......Page 257
7.2.2. Two Strategies ofAntigenic Variation Involving the G-H Loop ofFMDV......Page 258
7.2.3. Antigenic Variation and Restrictions to Genetic Variation in Sites Independent of the G-H Loop......Page 259
7.2.5. Conclusion: High Antigenic Divergence Through Limited Sequence Variation in the FMDV Capsid......Page 260
References......Page 261
1. Introduction: The Impact of Genetic Variation of RNA Viruses......Page 271
1.1. Molecular Basis of Genetic Variation of RNA Viruses......Page 272
1.2. Quasispecies Dynamics of RNA Viruses......Page 275
2.1. A Historical Introduction......Page 276
2.2. The Genetic and Antigenic Heterogeneity of FMDV......Page 277
2.3. Antigenic Variation in the Absence of Immune Selection......Page 279
2.4. Variations of Host Cell Tropism......Page 280
3. Natural Evolution of FMDV......Page 282
3.1. Phylogenetic Relationships Among FMDVs: Epidemiological Fitness......Page 283
3.2. Molecular Epidemiology, Sequence Clouds and Determinants of Phenotype......Page 285
3.3. Rates of Evolution of FMDV as Compared with Other RNA Viruses......Page 287
4.1. Memory in FMDV Quasispecies......Page 291
4.1.2. Biological Implications of Quasispecies Memory......Page 293
4.2.1 Resistance of FMDV to Extinction Despite Accumulation of Mutations by Repeated Bottleneck Events......Page 294
4.2.2. FMDV Extinction Through Lethal Mutagenesis or the Transition into Error Catastrophe......Page 296
5. Summary, Conclusions and Prospects......Page 299
References......Page 301
1. Introduction......Page 315
2. History of FMD-Vaccine Production......Page 316
2.2. Frenkel Vaccines......Page 317
2.3. Virus Production in (Primary) Monolayer Cells......Page 320
2.5. Further Developments in Europe and South America......Page 321
3.2. Quality Assurance and Quality Control......Page 323
4.1. Medium and Serum......Page 324
4.3. Selection of Vaccine Strains......Page 326
5. In Process Controls......Page 327
5.3. Quantitative Sucrose Density Gradient Analysis......Page 328
7. Virus Production......Page 329
8. Inactivation and \'In Process\' Safety Testing......Page 330
9. Concentration and Purification of the Antigen......Page 331
9.4. Precipitation with Polyethylene Glycol (PEG)......Page 332
10.2. Oil Adjuvant Vaccines......Page 333
11.1. Safety......Page 334
11.2. Potency and Duration of Immunity......Page 335
13. Performance of Emergency Vaccines......Page 336
15. World-Wide Eradication of FMD?......Page 337
References......Page 338
1. History of Foot-and-Mouth Disease Vaccines......Page 344
2. The Antigenic Structure of FMDV - Early Studies......Page 346
3. Synthetic Peptides Induce Protection Against FMD......Page 348
4. Structure of FMDV-Explanation for the Immunogenicity of the VP1 G-H Loop......Page 351
5. Structure and Function of the VP1 G-H Loop......Page 354
6. Peptide Vaccines-Improvements in Antigen Presentation......Page 355
7. Comparative Efficacies of Peptide Vaccines in Different Species......Page 357
References......Page 358
1. Introduction......Page 364
2.1. Types of Model......Page 366
2.2. Compartments......Page 368
2.3. Parameters and Variables......Page 369
2.4. Quantifying Transmission......Page 370
3.1. Different Host Types......Page 371
3.2. Spatial Effects......Page 372
4.1. Parameter Estimation......Page 374
4.3. Sensitivity Analysis and Validation......Page 376
4.4. Results of Model Fitting......Page 377
5.2. Movement Restrictions......Page 378
5.3. Stamping Out......Page 379
5.5. Reactive Vaccination......Page 380
5.6. Prophylactic Vaccination......Page 381
6. An Example: The Keeling Model......Page 382
7. Future of Mathematical Models......Page 385
8. Acknowledgements......Page 386
References......Page 387
1. Introduction......Page 391
2. African Buffalo Syncerus caffer: The Maintenance Host of the SAT Types FMDV......Page 392
2.2 Maintenance of SAT Viruses in Buffalo Populations......Page 393
3. Genetic Diversity of FMDV Derived from Buffalo in Southern Africa......Page 395
4. Ability of Acutely and Persistently Infected Buffalo to Transmit SAT Viruses to Cohorts......Page 398
4.1 Transmission of SAT Viruses from Buffalo to Other Species......Page 399
5. The Role of Wildlife Species Other Than Buffalo in the Epidemiology of FMD in Southern Africa......Page 403
5.1 Clinical Signs of FMD in Wildlife......Page 405
6. Control of FMD in Sub-Saharan Africa Where Wildlife are Involved......Page 406
6.1 Fencing and Control of Translocation......Page 407
6.2 Vaccination......Page 409
6.3 Establishment of Disease-Free Buffalo Herds......Page 411
References......Page 412
1. Introduction......Page 419
2. Definition of an Outbreak......Page 420
3. Laboratory Diagnosis of FMD......Page 422
4. Persistent Infection......Page 423
5. Antibody in Saliva......Page 424
6. Non Structural Proteins (NSPs)......Page 425
7. Pen-Side Tests......Page 426
8. Control......Page 427
References......Page 430
1. Introduction......Page 433
2. Disease Reporting......Page 434
4. FMD Diagnosis and Research......Page 435
5. Standardisation of FMD Vaccine Production and Control......Page 436
6.1. Buffer Zone in Turkey......Page 437
6.3. FMD Control in the Caucasus Region in 1999 and 2000......Page 439
7. International Support to FMD Control Programmes......Page 440
8. Conclusion......Page 442
9. References......Page 443
ANNEX......Page 444
1. Introduction......Page 445
3. Eradication of FMD......Page 446
4. Emergence of the PanAsia Strain......Page 447
6. Emergence of Viruses With Altered Host Range......Page 448
8. Recent Outbreaks of Other FMD Types......Page 449
9.1. Genetic and Biological Factors......Page 450
9.4. Social, Political and Economic Factors......Page 451
10. Conclusions......Page 452
References......Page 453
Colour Plates......Page 455