Marek's Disease (eBook)

Cover 1
Biology of animal infections 3
Marek’s disease: an evolving problem 4
Dedication 6
Contents 8
Contributors 14
Series Introduction 16
Preface 18
Acknowledgements 20
Abbreviations 22
1 Introduction 24
General background 24
József Marek (1868–1952) and the identification of the disease 25
Houghton Poultry Research Station and the isolation of the causative agent of Marek's disease 27
The place of Marek's disease and Marek's disease virus in the biological sciences 29
Acknowledgements 30
References 30
2 Marek's disease: long and difficult beginnings 31
Introduction 31
Early days 31
Terminology and classification 32
Evidence for the separation of Marek's disease from lymphoid leukoses 33
Clinical and pathological studies of field cases 33
Transmission studies 34
Lymphoid leukosis 34
Marek’s disease 34
Experimental studies comparing Marek's disease with lymphoid leukosis 35
Identifying the Marek's disease virus 35
Identification of Marek's disease herpesvirus 36
Circumstantial evidence 36
Definitive evidence 37
Summary 38
References 38
3 The genome content of Marek's disease-like viruses 40
Introduction 40
Gene content and transcription of the Mardiviruses 41
Transcription and gene expression during MDV latency 48
Manipulation of the MDV genome: new strategy using bacterial artificial chromosomes 50
Summary 52
Acknowledgements 52
References 52
4 Marek's disease virus oncogenicity: molecular mechanisms 55
Introduction 55
Meq, a Jun/Fos family member, as a putative oncogene for MDV 56
The structure and function of Meq 57
Structure 57
Transactivation 57
Dimerization in vitro and in vivo 58
DNA and chromosomal binding 58
Interactions with cellular factors 59
Meq as a transcriptional regulator 60
Meq as a transforming protein 61
Meq as a major oncoprotein in MDV oncogenesis 62
Meq mutations in proline-rich domains correlate with virulence 63
Meq's potential roles in MDV replication and latency 64
Summary and implications of Meq as an oncogene for MDV 65
Other genes associated with pathogenicity 66
BamHI-H family of transcripts 67
MDV phosphoprotein 38 (pp38) complex 67
MDV-encoded CXC chemokine, vIL-8 67
MDV-encoded telomerase RNA 68
MDV ICP4 homologue-related transcripts 69
Summary 69
References 70
5 Marek's disease: a worldwide problem 72
Introduction 72
Diagnostic investigation of MD problems 74
Economic impact 76
Causes of outbreaks 77
MD in species other than chickens 83
Problems associated with contamination of MD vaccines 83
Summary 83
References 84
6 Marek's disease virus: biology and life cycle 85
Introduction 85
Natural infection with MDV 88
Early cytolytic phase 89
Latency 92
Late cytolytic phase 94
Fully productive infection in the feather-follicle epithelium 94
Transformation 95
Conclusions 98
Acknowledgements 99
References 99
7 Pathological responses to infection 101
Introduction 101
Virus–cell relationships in Marek's disease 102
Pathogenesis and pathology of Marek's disease 102
Primary infection 102
Acute cytolytic infection of lymphoid tissue 104
Viraemia and haematology 105
Infection of feather-follicle epithelium 106
Infection of other parenchymatous tissues 107
Peripheral neuropathy 107
Central nervous system 111
Lymphomatosis 112
Atherosclerosis 114
Ocular changes 115
Factors affecting lesion type 115
Virus strain 115
Host 116
Marek's disease in other species 117
Turkeys 117
Japanese quail 118
Pheasants 118
Conclusions 118
References 119
8 Marek's disease lymphomas 121
Introduction 121
Histopathology 122
Peripheral nerves 122
Skin 122
Visceral and skeletal muscle lymphomas 122
Lymphoma cell phenotypes 123
MATSAs 123
MDV-transformed cells 124
Phenotypes of MD lymphoma cells 124
MDV genome 125
The cellular environment 125
The identity of the neoplastically transformed cells in MD lymphomas 126
Anti-lymphoma immunity 128
MD lymphoma regression 128
Anti-MD lymphoma immunity 129
Transplantable tumours 129
Tumour antigens in MD 130
Model for MD lymphomagenesis 131
Summary 132
Acknowledgements 133
References 133
9 Genetic resistance to Marek's disease 135
Introduction 135
MHC associated resistance 136
Structure and function of the MHC 137
Mechanism of MHC-determined resistance to MD 149
Non-MHC associated resistance 150
Differences in viral replication between lines 6 and 7 150
Phenotypic comparisons 151
Investigation of candidate genes 152
Genomic mapping approaches 152
Conclusions 154
Acknowledgements 155
References 155
10 Immunity to Marek's disease 158
Introduction 158
MDV entry via the lungs 159
Role of macrophages 160
Role of natural killer cells 161
Acquired immune responses to MDV 163
Role of antibodies 163
Role of cell-mediated immune responses 164
Cytokine responses during the cytolytic phase 166
The role of cytokines in the induction and maintenance of latency 167
Cytokine production by tumour cells 167
Role of the MDV-encoded CXC chemokine 168
Immunity to MDV induced by vaccination 169
Conclusions 171
References 171
11 Marek's disease immunosuppression 174
Introduction 174
Mechanisms of MD-induced immunosuppression 175
Immunosuppression caused by loss of lymphocytes 175
Immunosuppression caused by changes in the regulation of immune responses 178
Nitric oxide, a dual role 178
Cytokines 179
Down-regulation of lymphocyte surface molecules and other immuno-evasive mechanisms 179
Immunosuppression caused by tumour cells 180
Confounding factors in MDV-induced immunosuppression 181
Chicken infectious anaemia virus 181
Infectious bursal disease virus 182
Reticuloendotheliosis virus 182
Reovirus infection 182
Consequences of immunosuppression 183
Summary 184
References 184
12 Diagnosis of Marek's disease 188
Introduction 188
Diagnosis of MD under field conditions 189
Laboratory diagnosis of MD 191
Collection of infectious material for in vitro studies 191
Virus isolation and identification 192
Detection and characterization of MDV antigens and antibodies 193
Identification of MDV DNA 194
Differentiation of MDV serotypes, strains and isolates 195
Summary 197
References 197
13 Vaccination against Marek's disease 200
History of Marek's disease vaccine 200
Importance of vaccination 202
Licensing, manufacturing and administering current MD vaccines 203
In ovo vaccination 204
Vaccination problems and solutions 206
Attenuation of MDV and its effect on protection 208
Recombinant vaccines 211
Summary 214
References 214
14 Future strategies for controlling Marek's disease 218
Introduction 218
Current MD situation and vaccination strategies 219
Future risk of increasing the incidence of MD 220
Current tools for MD control 221
Vaccination 221
Genetics 222
Biosecurity 223
Developing new strategies for control 223
Vaccine development 223
Development of transgenic chickens 225
What research is needed for the rational development of new strategies of control? 226
Summary 228
Acknowledgements 230
References 230
15 Conclusions 232
References 236
Appendix: Key references 237
Index 239
A 239
B 239
C 239
D 240
E 240
F 240
G 240
H 240
I 240
J 241
K 241
L 241
M 241
N 243
O 243
P 243
Q 243
R 243
S 243
T 243
V 244
Colour plates 140