| Series Introduction | p. xv |
| Preface | p. xix |
| Acknowledgement | p. xxi |
| Introduction | p. 1 |
| Background | p. 1 |
| Bluetongue, an emerging disease | p. 2 |
| The history of bluetongue | p. 7 |
| Introduction | p. 7 |
| Geographical distribution | p. 7 |
| Host range | p. 9 |
| Aetiology | p. 11 |
| Transmission | p. 13 |
| Control | p. 14 |
| Bluetongue virus, other orbiviruses and other reoviruses: Their relationships and taxonomy | p. 23 |
| Introduction | p. 23 |
| The genera of the family Reoviridae | p. 28 |
| The genus Orbivirus | p. 29 |
| Classification and differentiation of the Orbivirus species | p. 30 |
| The economically important orbiviruses | p. 32 |
| Bluetongue | p. 32 |
| African horse sickness | p. 32 |
| Epizootic haemorrhagic disease | p. 33 |
| Equine encephalosis virus | p. 34 |
| Emerging orbiviruses | p. 35 |
| Orbiviruses that can infect humans | p. 36 |
| Relationships with other reoviruses | p. 37 |
| Phylogenetic relationships of the orbivirus proteins | p. 39 |
| Phylogenetic relationships between the RNA- dependent RNA polymerase (Pol - RdRP) of the different orbiviruses | p. 43 |
| Phylogenetic relationships based on the sub-core shell T2 protein of bluetongue virus and other orbiviruses | p. 44 |
| Dating divergence times for bluetongue virus and epizootic haemorrhagic disease virus serotypes | p. 46 |
| Bluetongue virus replication and assembly | p. 53 |
| Introduction | p. 53 |
| Arrangement of proteins in the virus outer capsid and their role in virus entry | p. 54 |
| Functional dissection of the enzymatic core proteins | p. 57 |
| Assembly of the viral core | p. 61 |
| Assembly of the viral outer capsid | p. 66 |
| Release of progeny virions from infected cells | p. 67 |
| Concluding remarks | p. 71 |
| Bluetongue virus: cell biology | p. 77 |
| Introduction | p. 77 |
| Bluetongue virus entry into the cellular host | p. 78 |
| Viral structures and their functions | p. 81 |
| Viral inclusion bodies | p. 83 |
| NS1 Tubules | p. 86 |
| Interaction of bluetongue virus with the cytoskeleton | p. 87 |
| Involvement of the cellular translation machinery during bluetongue virus infection | p. 88 |
| Fate of bluetongue virus-infected cells and virus egress | p. 89 |
| Conclusions | p. 94 |
| The structure of bluetongue virus core and proteins | p. 101 |
| Introduction | p. 101 |
| The bluetongue virion structure | p. 102 |
| Genome packaging | p. 105 |
| Enzyme functions and location | p. 108 |
| Substrate and product-binding sites | p. 110 |
| Site X: the exit | p. 113 |
| Site N: entry | p. 114 |
| Sites I: inter-trimer | p. 115 |
| Sites F and C: anion and cation | p. 115 |
| Binding of dsRNA to the bluetongue virus core surface | p. 116 |
| VP4: The 'capping' enzyme | p. 117 |
| Bluetongue virus outer capsid proteins VP2 and VP5 | p. 120 |
| Bluetongue virus non-structural proteins | p. 121 |
| Bluetongue virus particle structure and cell entry mechanisms | p. 125 |
| Molecular epidemiology studies of bluetongue virus | p. 135 |
| Introduction | p. 135 |
| Variable and conserved genome segments | p. 137 |
| BTV outer-capsid protein genes | p. 137 |
| BTV core-protein genes | p. 143 |
| BTV non-structural protein genes | p. 146 |
| BTV incursions into Europe | p. 146 |
| BTV-1 | p. 147 |
| BTV-2 | p. 148 |
| BTV-4 | p. 150 |
| BTV-8 | p. 151 |
| Single nucleotide polymorphism analysis | p. 152 |
| BTV-9 | p. 152 |
| BTV-15 | p. 153 |
| BTV-16 | p. 154 |
| Phylogenetic analyses of BTV core/non-structural proteins and identification of reassortants | p. 155 |
| Conclusions/Discussion | p. 156 |
| Bluetongue in the Indian subcontinent | p. 167 |
| Introduction | p. 167 |
| Geographical distribution and seasonality | p. 168 |
| Clinical bluetongue in sheep | p. 170 |
| Serological prevalence of bluetongue in other animal species | p. 176 |
| Goats | p. 176 |
| Cattle and buffalo | p. 177 |
| Camels | p. 179 |
| Wild ruminants | p. 179 |
| Other species | p. 180 |
| Vectors | p. 180 |
| Bluetongue virus serotypes reported from Indian subcontinent | p. 182 |
| Diagnosis | p. 184 |
| Virus isolation | p. 184 |
| Immunological detection of virus | p. 186 |
| Nucleic acid-based diagnosis | p. 186 |
| Molecular epidemiology studies | p. 186 |
| Economic impact of bluetongue and control | p. 187 |
| Acknowledgments | p. 189 |
| Current status of bluetongue virus in the Americas | p. 197 |
| Introduction | p. 197 |
| North America | p. 198 |
| Disease status in domestic and wild ruminants | p. 198 |
| Status of virus types | p. 200 |
| Status of insect vectors | p. 201 |
| Economic impact | p. 205 |
| Control strategies | p. 205 |
| Central America | p. 205 |
| Disease status in domestic and wild ruminants | p. 205 |
| Status of virus types | p. 206 |
| Status of vector species | p. 206 |
| South America | p. 207 |
| Disease status in domestic and wild ruminants | p. 207 |
| Status of virus types | p. 209 |
| Status of vector species | p. 209 |
| Economic impact | p. 210 |
| Control strategies | p. 210 |
| Virus-vector Interactions | p. 210 |
| Summary | p. 212 |
| Acknowledgments | p. 212 |
| Bluetongue viruses in Australasia and East Asia | p. 223 |
| Introduction | p. 223 |
| Major studies of bluetongue virus in the region | p. 224 |
| Bluetongue disease in Australasia and East Asia | p. 225 |
| Bluetongue virus serotypes isolated in the region | p. 226 |
| The bluetongue virus genotypes in the region | p. 229 |
| The known and suspected Culicoides spp vectors | p. 230 |
| Conclusions | p. 230 |
| Bluetongue in Europe and the Mediterranean Basin | p. 235 |
| Introduction | p. 235 |
| Bluetongue virus in the Mediterranean Basin, 1998-2005 | p. 236 |
| Bluetongue virus in Greece, Turkey, the Balkans, Cyprus and Israel | p. 236 |
| Bluetongue virus in North Africa, Italy, France, Spain and Portugal | p. 242 |
| Origins of the outbreaks | p. 247 |
| Vector species of Culicoides in Europe and the Mediterranean Basin | p. 250 |
| Bluetongue virus in Europe in 2006 and 2007 | p. 252 |
| Mechanisms of overwintering | p. 254 |
| Summary | p. 256 |
| Bluetongue virus in the mammalian host and the induced immune response | p. 265 |
| Introduction | p. 265 |
| Bluetongue virus infection of the ruminant host | p. 266 |
| Bluetongue virus replication in the ruminant host | p. 267 |
| Cellular targets | p. 267 |
| Organ tropism | p. 270 |
| Immune response | p. 273 |
| Humoral immune response | p. 273 |
| Cellular immune response | p. 274 |
| A potential bluetongue virus overwintering mechanism in the ruminant host | p. 275 |
| Conclusive remarks | p. 277 |
| Clinical signs and pathology | p. 285 |
| Introduction | p. 285 |
| Clinical signs | p. 286 |
| The pathogenesis of bluetongue virus infection | p. 288 |
| Persistent bluetongue virus infection of cattle | p. 290 |
| Bluetongue in other animal species | p. 291 |
| Bluetongue virus in the insect host | p. 295 |
| Introduction | p. 295 |
| Culicoides biting midges | p. 296 |
| Bluetongue virus | p. 296 |
| Vector species of Culicoides | p. 297 |
| Africa | p. 297 |
| Asia | p. 298 |
| Australasia | p. 299 |
| The Americas | p. 299 |
| Europe | p. 300 |
| Infection and replication of bluetongue virus in vector Culicoides | p. 301 |
| Bluetongue virus infection and susceptibility rates in vector species of Culicoides | p. 303 |
| Barriers to the infection, dissemination and transmission of arboviruses in insect vectors | p. 305 |
| Barriers to the infection of vector Culicoides with bluetongue virus | p. 305 |
| A possible overwintering mechanism of bluetongue virus in vector Culicoides | p. 307 |
| Effects of temperature on arbovirus infection and transmission by insect vectors | p. 309 |
| Effect of temperature on bluetongue virus infection by vector Cluicoides | p. 309 |
| Effects of temperature on bluetongue virus infection and transmission by 'non-vector' Culicoides | p. 310 |
| Other factors influencing the infection of Culicoides with bluetongue virus | p. 311 |
| Summary | p. 312 |
| Rates of bluetongue virus transmission between Culicoides sonorensis and sheep | p. 321 |
| Introduction | p. 321 |
| Materials and methods | p. 323 |
| Experiment I: vector to host (V to H) transmission | p. 323 |
| Experiment II: host to vector (H to V) transmission | p. 325 |
| Midge virus titration assay | p. 326 |
| Blood virus titration assays | p. 327 |
| Antibody detection ELISA | p. 327 |
| Results | p. 327 |
| Experiment I: vector to host (V to H) transmission | p. 327 |
| Experiment II: host to vector (H to V) transmission | p. 334 |
| Discussion | p. 337 |
| Acknowledgements | p. 340 |
| Bluetongue virus and climate change | p. 343 |
| Introduction | p. 343 |
| The shifting pattern of European bluetongue epidemics | p. 344 |
| Evidence linking patterns in bluetongue to climate change | p. 347 |
| Non-climatic (biotic and abiotic) factors unlikely to influence bluetongue distribution in Europe | p. 347 |
| Biological sensitivity of bluetongue virus and Culicoides to climate | p. 348 |
| Spatio-temporal correspondence between changes in European climate and changes in bluetongue virus | p. 349 |
| Extended distribution of the major Old World vector, C. imicola | p. 350 |
| Involvement of Palearctic vectors in bluetongue virus transmission in Europe | p. 351 |
| Why is the bluetongue virus-Culicoides episystem responsive to climate change? | p. 355 |
| A global view of climate change and bluetongue epidemiology | p. 356 |
| Acknowledgements | p. 358 |
| Bluetongue virus diagnosis | p. 365 |
| Introduction | p. 365 |
| Clinical diagnosis | p. 369 |
| Clinical signs as an early indicator of BTV infection | p. 369 |
| Virus isolation | p. 370 |
| Antibody/antigen-based assays | p. 371 |
| Group-specific antibody detection assays | p. 371 |
| Group-specific antigen detection assays | p. 374 |
| Serotype-specific antibody/antigen assays | p. 374 |
| Serotype-specific antibody detection assays | p. 375 |
| Serotype-specific antigen detection assays | p. 376 |
| Molecular assays | p. 377 |
| The BTV genome | p. 377 |
| Group-specific molecular assays | p. 380 |
| Serotype-specific molecular assays | p. 383 |
| Detection of BTV in Culicoides midges | p. 384 |
| Ring-trials and proficiency testing | p. 386 |
| Diagnostic samples | p. 387 |
| The future | p. 388 |
| Bluetongue virus vaccines past and present | p. 397 |
| Introduction | p. 397 |
| Multiple BTV serotypes | p. 401 |
| Attenuated 'live' vaccines | p. 402 |
| History and efficacy | p. 402 |
| Concerns associated with attenuated BTV vaccines | p. 403 |
| Live vaccine 'platforms' | p. 407 |
| Inactivated BTV vaccines | p. 408 |
| Subunit vaccines | p. 409 |
| Virus-like particles | p. 409 |
| Individual BTV proteins as vaccine candidates | p. 411 |
| Differentiating infected from vaccinated animals | p. 414 |
| Expression of viral proteins for use as vaccine components | p. 415 |
| Adjuvants | p. 417 |
| Synthetic and biodegradable delivery systems | p. 418 |
| Regulations and acceptability | p. 419 |
| Concluding remarks | p. 420 |
| Bluetongue control strategies | p. 429 |
| Introduction | p. 429 |
| Risk factors | p. 430 |
| Climate and environment | p. 430 |
| The vectors | p. 431 |
| Vertebrate hosts | p. 432 |
| The BT virus | p. 433 |
| Methods of surveillance and monitoring | p. 434 |
| Clinical surveillance | p. 434 |
| Serological surveillance | p. 435 |
| Virological surveillance | p. 436 |
| Molecular methods for surveillance (RT-PCR and sequencing) | p. 436 |
| Entomological surveillance | p. 437 |
| Modelling | p. 438 |
| Methods of control | p. 438 |
| Zoosanitary methods - Animal movement restrictions | p. 438 |
| Husbandry modifications | p. 439 |
| Vector abatement and/or control | p. 439 |
| Vaccination | p. 440 |
| Stamping out | p. 441 |
| Control strategies | p. 441 |
| Endemic situations | p. 442 |
| Incursion threats into BTV-free countries | p. 442 |
| Epidemic situations (first or re-introductions) | p. 442 |
| International legislation | p. 445 |
| OIE guidelines | p. 445 |
| European Union legislation | p. 446 |
| Conclusions | p. 453 |
| Glossary | p. 459 |
| Index | p. 465 |
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