1. Introduction: subacute spongiform virus encephalopathies from the perspective of a neuroscientist.- 2. The molecular biology of the slow viruses.- 2.1. The search for the virus-specific nucleic acid.- 2.1.1. Radiation experiments.- 2.1.2. Fruitless attempts to isolate scrapie-specific infectious nucleic acid.- 2.2. The prion protein.- 2.2.1. The purification of the PrP 27-30, PrP 33-35SC and PrP 33-35C.- 2.2.1.1. Strategies used to purify the scrapie virus and scrapie specific protein.- 2.2.1.2. Purification of the PrP27-30.- 2.2.1.3. PrP proteins are disease-specific for the whole group of unconventional slow virus disorders.- 2.2.1.4. PrP 33-35SC and PrP 33-35C.- 2.2.2. The structure of the PrP proteins.- 2.2.2.1. N-terminal sequence of the PrP.- 2.2.2.2. The secondary structure of the PrP.- 2.2.3. Postranslational modifications of the PrP.- 2.2.4. Functional studies of the PrP proteins.- 2.2.5. The scrapie associated fibrils or prion rods.- 2.2.5.1. The chemical composition of SAF.- 2.3. The structure of the gene encoding PrP 33-35 (Prn-p) in different species.- 2.3.1. The hamster Prn-p gene.- 2.3.2. The murine Prn-p gene.- 2.3.3. The rat Prn-p gene.- 2.3.4. The human Prn-p gene (PRNP).- 2.3.5. The ovine and bovine Prn-p gene.- 2.3.6. The avian analogue of the Prn-p gene.- 2.3.7. The linkage of genes controlling the incubation period and susceptibility to scrapie and Creutzfeldt-Jakob disease (CJD) to the gene encoding PrP 33-35 (Prn-p).- 2.3.7.1. Prn-i and Sinc in mice.- 2.3.7.2. Prn-i and Sip gene in sheep.- 2.3.8. The linkage of Gerstmann-Sträussler-Scheinker syndrome (GSSS) to the PrP (PRNP) gene.- 2.3.9. Familial CJD.- 2.3.10. The association of CJD cases of Eastern European origin and in Sephardic Jews with a mutation of the PrP gene at codon 200.- 2.3.11 Other PrP gene mutations associated with sporadic and familial CJD cases.- 2.3.12 A 0.15kb insertion within the PrP gene observed with CJD and GSSS cases.- 2.3.13 The codon 178 mutation in familial CJD.- 2.4. The models of slow viruses.- 2.4.1. Strains of scrapie virus.- 2.4.2. The prion-only hypothesis.- 2.4.3. Virino and conventional virus hypothesis.- 3. The pathogenesis of slow virus infection.- 3.1. The general sequence of the pathogenetic events.- 3.2. The role of the spleen.- 3.3. The role of the spleen in neuroinvasion.- 3.4. The role of viremia.- 3.5. The role of macrophages in scrapie infection.- 3.6. The neural spread of infectivity from the spleen to the central nervous system.- 3.7. The neural spread of infectivity within the central nervous system.- 3.8. Biochemistry and histochemistry of slow virus infections.- 3.8.1. Neurotransmitters alterations.- 3.8.1.1. Cholinergic system.- 3.8.1.2. Monoaminergic systems.- 3.8.1.3. Histaminergic system.- 3.8.1.4. GABAergic system.- 3.8.2. Oxydative and lysosomal enzymes.- 3.8.2. Immunology of slow virus infections.- 3.8.2.1. Autoantibodies against neuroflament proteins.- 3.8.2.2. Increased concentration of IgG in serum of scrapie- affected sheep.- 4. Neuropathology of slow virus diseases Ill.- 4.1. Natural scrapie.- 4.2. Kuru.- 4.3. Creutzfeldt-Jakob disease (CJD).- 4.3.1. Introduction.- 4.3.2. Classifications.- 4.3.3. Classical CJD.- 4.3.4. Ataxic form of CJD.- 4.3.5. Gerstmann-Sträussler-Scheinker (GSS) syndrome.- 4.3.6. Panencephalopathic form of CJD.- 4.3.7. Amyotrophic form of CJD.- 4.3.8. CJD and other neurological disorders.- 4.4. Elements of neuropathology of slow virus disorders.- 4.4.1. Spongiform vacuoles.- 4.4.1.1. Introduction.- 4.4.1.2. Distribution of vacuoles within grey and white matter: lesion profile.- 4.4.1.3. Ultrastructure of vacuoles.- 4.4.1.3.1. Creutzfeldt-Jakob disease (CJD).- 4.4.1.3.2. Scrapie, bovine spongiform encephalopathy (BSE) and chronic wasting disease.- 4.4.1.3.3. Ultrastructure of intramyelin vacuoles in the panencephalopathic type of CJD and other types of subacute spongiform virus encephalopathies.- 4.4.1.4. Morphogenesis of spongiform changes.- 4.4.2. Astrocytic reaction.- 4.4.2.1. Introduction.- 4.4.2.2. Kuru, Creutzfeldt-Jakob disease and Gerstmann- Sträussler-Scheinker syndrome.- 4.4.2.2.1. Kuru.- 4.4.2.2.2. Creutzfeldt-Jakob disease (CJD) and Gerstmann- Sträussler-Scheinker syndrome (GSSS).- 4.4.2.2.3. The involvement of astrocytes in formation of amyloid plaques.- 4.4.2.4. Scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease.- 4.4.2.5. The blood-brain-barrier in slow virus diseases.- 4.4.2.6 The particular forms of astrocytic reaction in unconventional slow virus diseases.- 4.4.2.7. Expression of glial fibrillary acidic protein (GFAP).- 4.4.3. The neuropathology of amyloid plaque.- 4.4.3.1. Kuru.- 4.4.3.2. Creutzfeld-Jakob-disease CJD.- 4.4.3.3. Gerstmann-Stràussler-Scheinker (GSS) syndrome.- 4.4.3.4. Scrapie and bovine spongiform encephalopathy and chronic wasting disease.- 4.4.3.5. The biology of amyloid plaques.- 4.4.3.5.1. The biology of amyloid plaques; the correlation between the number of amyloid plaques and strain of virus, inoculation route and aging.- 4.4.3.5.2. The immunohistochemistry of amyloid plaques.- 4.4.3.5.3. The relation of amyloid plaques to neuroaxonal dystrophy.- 4.4.4. Tubulovesicular structures.- 4.4.4.1. Introduction.- 4.4.4.2. "Virus-like particles" of unknown significance.- 4.4.3. Tubulovesicular structures.- 4.4.5. Neuroaxonal dystrophy.- 4.4.5.1. Neuroaxonal dystrophy: a common form of neuronal degeneration.- 4.4.5.2. Neuroaxonal dystrophy in subacute spongiform virus encephalopathies.- 4.4.6. Different forms of neuronal degeneration in slow virus disorders.- 4.4.6.1. The degeneration and neuronal loss.- 4.4.6.2. Intranuclear eosinophilic inclusions.- 4.4.6.3. Spiroplasma-like inclusions.- 4.4.6.4. Cerebellar lamellar bodies.- 4.4.6.5. Intraneuronal inclusions in bovine spongiform encephalopathy.- 4.4.6.6. Autophagic vacuoles in Creutzfeldt-Jakob disease and scrapie.- 5. Final conclusions.- Addendum.- References.

Scrapie, a naturally occurring neurodegenerative disease of sheep and sometimes goats, is a prototypic disease for the whole group of the subacute spongiform virus encephalopathies. Kuru was the first human disease of this type to be discovered in 1957 by Gajdusek and Zigas, and its discovery opened the whole field in the human biomedical sciences by the very realization of the fact that viruses may induce disease months or even decades after infections, and that these slow virus diseases are more compatible with classical degenerations of the nervous system than with inflammatory disorders of the brain. More than a quarter of a century since discovery of Kuru, and more than half a century following the first transmission of scrapie, the very nature of the infectious virus remains unknown.
This comprehensive review covers all aspects of slow unconventional virus infections known today. It includes numerous historical data, biochemistry and molecular biology of the prion protein and its gene, the role of genetics and mutations within PrP gene, spreading and targeting of the virus, biochemistry and neurochemistry of the alterations of different neurotransmitter system and neuropathology. More than 1000 references are listed and critically analyzed; the reader can find references to all experiments and laboratory findings which has ever been done in this field. Furthermore, the book offers different view on the basic problems as for example, the nature of the scrapie agent.