Contributors | p. xiii |
Series Introduction | p. xv |
Preface | p. xvii |
Acknowledgements | p. xix |
Abbreviations | p. xxi |
Introduction | p. 1 |
General background | p. 1 |
Jozsef Marek (1868-1952) and the identification of the disease | p. 2 |
Houghton Poultry Research Station and the isolation of the causative agent of Marek's disease | p. 4 |
The place of Marek's disease and Marek's disease virus in the biological sciences | p. 6 |
Acknowledgements | p. 7 |
References | p. 7 |
Marek's disease: long and difficult beginnings | p. 8 |
Introduction | p. 8 |
Early days | p. 8 |
Terminology and classification | p. 9 |
Evidence for the separation of Marek's disease from lymphoid leukoses | p. 10 |
Clinical and pathological studies of field cases | p. 10 |
Transmission studies | p. 11 |
Experimental studies comparing Marek's disease with lymphoid leukosis | p. 12 |
Identifying the Marek's disease virus | p. 12 |
Identification of Marek's disease herpesvirus | p. 13 |
Circumstantial evidence | p. 13 |
Definitive evidence | p. 14 |
Summary | p. 15 |
References | p. 15 |
The genome content of Marek's disease-like viruses | p. 17 |
Introduction | p. 17 |
Gene content and transcription of the Mardiviruses | p. 18 |
Transcription and gene expression during MDV latency | p. 25 |
Manipulation of the MDV genome: new strategy using bacterial artificial chromosomes | p. 27 |
Summary | p. 29 |
Acknowledgements | p. 29 |
References | p. 29 |
Marek's disease virus oncogenicity: molecular mechanisms | p. 32 |
Introduction | p. 32 |
Meq, a Jun/Fos family member, as a putative oncogene for MDV | p. 33 |
The structure and function of Meq | p. 34 |
Meq as a transcriptional regulator | p. 37 |
Meq as a transforming protein | p. 38 |
Meq as a major oncoprotein in MDV oncogenesis | p. 39 |
Meq mutations in proline-rich domains correlate with virulence | p. 40 |
Meq's potential roles in MDV replication and latency | p. 41 |
Summary and implications of Meq as an oncogene for MDV | p. 42 |
Other genes associated with pathogenicity | p. 43 |
BamHI-H family of transcripts | p. 44 |
MDV phosphoprotein 38 (pp38) complex | p. 44 |
MDV-encoded CXC chemokine, vIL-8 | p. 44 |
MDV-encoded telomerase RNA | p. 45 |
MDV ICP4 homologue-related transcripts | p. 46 |
Summary | p. 46 |
References | p. 47 |
Marek's disease: a worldwide problem | p. 49 |
Introduction | p. 49 |
Diagnostic investigation of MD problems | p. 51 |
Economic impact | p. 53 |
Causes of outbreaks | p. 54 |
MD in species other than chickens | p. 60 |
Problems associated with contamination of MD vaccines | p. 60 |
Summary | p. 60 |
References | p. 61 |
Marek's disease virus: biology and life cycle | p. 62 |
Introduction | p. 62 |
Natural infection with MDV | p. 65 |
Early cytolytic phase | p. 66 |
Latency | p. 69 |
Late cytolytic phase | p. 71 |
Fully productive infection in the feather-follicle epithelium | p. 71 |
Transformation | p. 72 |
Conclusions | p. 75 |
Acknowledgements | p. 76 |
References | p. 76 |
Pathological responses to infection | p. 78 |
Introduction | p. 78 |
Virus-cell relationships in Marek's disease | p. 79 |
Pathogenesis and pathology of Marek's disease | p. 79 |
Primary infection | p. 79 |
Acute cytolytic infection of lymphoid tissue | p. 81 |
Viraemia and haematology | p. 82 |
Infection of feather-follicle epithelium | p. 83 |
Infection of other parenchymatous tissues | p. 84 |
Peripheral neuropathy | p. 84 |
Central nervous system | p. 88 |
Lymphomatosis | p. 89 |
Atherosclerosis | p. 91 |
Ocular changes | p. 92 |
Factors affecting lesion type | p. 92 |
Virus strain | p. 92 |
Host | p. 93 |
Marek's disease in other species | p. 94 |
Turkeys | p. 94 |
Japanese quail | p. 95 |
Pheasants | p. 95 |
Conclusions | p. 95 |
References | p. 96 |
Marek's disease lymphomas | p. 98 |
Introduction | p. 98 |
Histopathology | p. 99 |
Peripheral nerves | p. 99 |
Skin | p. 99 |
Visceral and skeletal muscle lymphomas | p. 99 |
Lymphoma cell phenotypes | p. 100 |
MATSAs | p. 100 |
MDV-transformed cells | p. 101 |
Phenotypes of MD lymphoma cells | p. 101 |
The identity of the neoplastically transformed cells in MD lymphomas | p. 103 |
Anti-lymphoma immunity | p. 105 |
MD lymphoma regression | p. 105 |
Anti-MD lymphoma immunity | p. 106 |
Transplantable tumours | p. 106 |
Tumour antigens in MD | p. 107 |
Model for MD lymphomagenesis | p. 108 |
Summary | p. 109 |
Acknowledgements | p. 110 |
References | p. 110 |
Genetic resistance to Marek's disease | p. 112 |
Introduction | p. 112 |
MHC associated resistance | p. 113 |
Structure and function of the MHC | p. 114 |
Mechanism of MHC-determined resistance to MD | p. 117 |
Non-MHC associated resistance | p. 118 |
Differences in viral replication between lines 6 and 7 | p. 118 |
Phenotypic comparisons | p. 119 |
Investigation of candidate genes | p. 120 |
Genomic mapping approaches | p. 120 |
Conclusions | p. 122 |
Acknowledgements | p. 123 |
References | p. 123 |
Immunity to Marek's disease | p. 126 |
Introduction | p. 126 |
MDV entry via the lungs | p. 127 |
Role of macrophages | p. 128 |
Role of natural killer cells | p. 129 |
Acquired immune responses to MDV | p. 131 |
Role of antibodies | p. 131 |
Role of cell-mediated immune responses | p. 132 |
Cytokine responses during the cytolytic phase | p. 134 |
The role of cytokines in the induction and maintenance of latency | p. 135 |
Cytokine production by tumour cells | p. 135 |
Role of the MDV-encoded CXC chemokine | p. 136 |
Immunity to MDV induced by vaccination | p. 137 |
Conclusions | p. 139 |
References | p. 139 |
Marek's disease immunosuppression | p. 142 |
Introduction | p. 142 |
Mechanisms of MD-induced immunosuppression | p. 143 |
Immunosuppression caused by loss of lymphocytes | p. 143 |
Immunosuppression caused by changes in the regulation of immune responses | p. 146 |
Nitric oxide, a dual role | p. 146 |
Cytokines | p. 147 |
Down-regulation of lymphocyte surface molecules and other immuno-evasive mechanisms | p. 147 |
Immunosuppression caused by tumour cells | p. 148 |
Confounding factors in MDV-induced immunosuppression | p. 149 |
Chicken infectious anaemia virus | p. 149 |
Infectious bursal disease virus | p. 150 |
Reticuloendotheliosis virus | p. 150 |
Reovirus infection | p. 150 |
Consequences of immunosuppression | p. 151 |
Summary | p. 152 |
References | p. 152 |
Diagnosis of Marek's disease | p. 156 |
Introduction | p. 156 |
Diagnosis of MD under field conditions | p. 157 |
Laboratory diagnosis of MD | p. 159 |
Collection of infectious material for in vitro studies | p. 159 |
Virus isolation and identification | p. 160 |
Detection and characterization of MDV antigens and antibodies | p. 161 |
Identification of MDV DNA | p. 162 |
Differentiation of MDV serotypes, strains and isolates | p. 163 |
Summary | p. 165 |
References | p. 165 |
Vaccination against Marek's disease | p. 168 |
History of Marek's disease vaccine | p. 168 |
Importance of vaccination | p. 170 |
Licensing, manufacturing and administering current MD vaccines | p. 171 |
In ovo vaccination | p. 172 |
Vaccination problems and solutions | p. 174 |
Attenuation of MDV and its effect on protection | p. 176 |
Recombinant vaccines | p. 179 |
Summary | p. 182 |
References | p. 182 |
Future strategies for controlling Marek's disease | p. 186 |
Introduction | p. 186 |
Current MD situation and vaccination strategies | p. 187 |
Future risk of increasing the incidence of MD | p. 188 |
Current tools for MD control | p. 189 |
Vaccination | p. 189 |
Genetics | p. 190 |
Biosecurity | p. 191 |
Developing new strategies for control | p. 191 |
Vaccine development | p. 191 |
Development of transgenic chickens | p. 193 |
What research is needed for the rational development of new strategies of control? | p. 194 |
Summary | p. 196 |
Acknowledgements | p. 198 |
References | p. 198 |
Conclusions | p. 200 |
References | p. 204 |
Key references | p. 205 |
Index | p. 207 |
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