Subject Index

acetylcholine receptor 121 - inducing activity (ARIA) 110, 120 acquired immunodeficiency syndrome

(AIDS) 196 AD see Alzheimer's disease agent of replication 219 aggregation 203,214,217,218 - cooperativity 215 aldehydes 196 allotype barrier 247 Alzheimer's disease (AD) - amyloid 275 - early stages 275 - etiology 275 - plaques 275 - tangles 275 amines, quaternary 196 ammonium sulfate precipitation 46 amyloid 75,88,140, 197,275 - plaques 238 - rods 247 amyloidosis 69 antibodies, neutralizing 209 antigen 214 antigenicity 209 ARIA (acetylcholine receptor inducing ac­

tivity) 110, 120 astrocytes 259,268,269-272

bacteriophage MS2 206 bacterium 234 baculovirus vector 97, 98 bioassay 40,42-44,47,48 - accuracy 44 - observer bias 44 - solvent effects 44 biochemical markers for susceptibility - OLA haplotypes 173 - PrP gene RFLPs 173,174

blood 276 Borna disease 196 bovine spongiform encephalopathy (see

also encephalopathy) 21 brain pathology 127-130 - influence of scrapie strain 127-130,

136 - lesion - - profiles 127-129 - - targeting 127-130,136 - PrP accumulation 128,130,135,136 - vacuolation 127-129 BSE, possible source 33 buffy coat 276

C127 cells 95-98 carrier status 170, 176 - bioassay 176 cDNA librairies, construction 263-268 - screening, differential hybridization

261-263,265 - subtractive hybridization 266-268 centrifugation - density gradient 50 - - CsCI49 - - Nycodenz 49 - differential ultracentrifugation 47, 48 - discontinous sucrose gradient 46, 48 - rate zonal 50 chromatography - affinity 64 - exclusion 197,204,205 - lectin affinity 49, 50 chronic wasting disease 23 - historical 22 circovirus, porcine 199, 200 CJD see Creutzfeldt-Jakob disease CLAC hamsters 47 COS-7 cells 97, 98

282 Subject Index

Creutzfeldt-Jakob disease (CJD) 1, 233 - agent 49 - - CJD-like, contagious 279 - - density 50 - - in vitro replication 190 - - size 50 - - structural hypotheses 52 - clinical - - features 10 - - signs 25 - epidemiology 11-14 - experimental 278 - familial 219 - - Czechoslovakia 219 - - foci 219 - - Sephardic Jewish immigrants 220 - - susceptibility 219 - historical 22 - iatrogenic 15 - neuropatholgy 27 CsCI 49

dementia 276 detergent - extraction 46-48 - lipid-protein complexes (DLPCs) 246,

248 differential screening 211 disinfection 206, 208 DLPCs (detergent-lipid-protein complexes)

246,248 DNase I 211

electron microscopy 70, 221 - negative stain 221 - thin sections 221 encephalopathy, spongiform 276 - bovine 21 - - case definintion - - - clinical 23-25 - - - neuropathological 26, 27 - - clinical signs 23, 24 - - differential diagnosis 24 - - duration of illness 24 - - epidemiology 28-35 - - fibril demonstration 27 - - future course of the epidemic 34 - - incidence - - - age-specific 29,30 - - - annual in 1989 29 - - - epidemic curve 29 - - - geographical variation 32 - - - within-herd 30, 31 - - reasons of occurence 32, 33

- - route of exposure 31 - - source of infection 28, 32, 33 - experimental CJD 278 - repeat experiment 276 - subacute 1 - transmissible, origins 14, 15 endoglycosidase H 98, 100 environment 220 Epstein-Barr virus 175, 176 exclusion chromatography 197,204,205 experimental models - CH1641 171,173 - mice 169,170 - sheep 170,173 - SSBP/1 170, 171

filtration 197, 204, 205 formalin fixation 196 fractionation 213-215 Fukuoka-1 strain of CJD 69 fungus 234

gel electrophoresis 204, 206 genetic control of susceptibility - other diseases - - mouse hepatitis virus 175 - - mouse pox 174 - - street rabies virus 175 - scrapie 170-174 - - Cheviot sheep 170-174 - - Herwick sheep 171, 173 - - Swaledale sheep 171, 172 genetic disease 233 Gerstmann-Straussler syndrome

(GSS) 120,152,158,219,233 - susceptibility 219 Gerstmann-Straussler Scheinker

syndrome 1 - historical 22 glucose tolerance 142 glycolipid anchor 120 glycosidase digestion 49 Golgi apparatus 238 Gp34 39,49 GSS see Gerstmann-Straussler syndrome

hantavirus 209 heat exposures 196,207,208 hepadnaviruses 200 hepatitis - B 196,209 - delta agent 200 high salt extraction 47,48

host - adaption see scrapie strains - genetics of incubation period control - - Sinc 61,67 - - Sip 61 - - - linkage to PrP gene 61 - protein hypothesis, modified 52 hybridization - differential 261-263, 265 - in situ 62,63, 260, 261, 268-271 - subtractive 211, 266-268 hybridoma cultures 183, 186 hypochlorites 196, 207

Icelandic scrapie (rida) 168, 169 immune response 146 immunocytochemistry 260, 261, 268-271 immunogenicity 197,209 - no agent specific antibody 197 - noninflammatory 197 in situ hybridization 260, 261, 268-271 inactivation 206, 208 - kinetics 206 - purity 207 - vaccines 207 - water purification 207 incubation - period 126-127 - - influence of - - - scrapie strain 126, 127, 136 - - - host genotype 126,127,136 - time 219, 221 - - mice 155-158 Infectivity - association with membranes 58 - resistance to 58 - - detergents 58 - - proteases 58 - scrapie-associated fibrils (see also

SAF) 58 - - PrP monomers 59, 67 - - PrP oligomers 59, 67 - - ScPrP 68 - PrP-27-30 58 - protein/infectious particle ratio 58, 59 - SOS-PAGE 59 inoculation, stereotaxic 142, 143 interspecies transmission 130-132, 134,

135 iodophors 196

kinetics 215,217,218 kuru 1,3-9,233,238 - clinical course 4, 5

Subject Index 283

- epidemiology 7 - etiology 8, 9 - historical 22 - incidence rate 4 - pathology 6 - route of exposure 31

lectin affinity chromatography 49, 50 liposomes 248 LVG hamsters 47

micrococcal nuclease 47,211 Mission Texas experiment 167,168 mitoplast(s) 213, 214 - fraction 49 modified host protein hypothesis 52 mouse - hepatitis virus 175 - pox 174 mRNA 211 multimeric structures 215 mutation 196, 211, 213, 220, 221

nature of agent, theories 140, 149 neuroblastoma cells 98-104 neuropathology, molecular 259-261,

268-272 neutralizing antibodies 209 non-A hepatitis 196 non-B hepatitis 196 nuclease 210 - digestion 46, 48 - - micrococcal nuclease 47 - resistance 197 Nycodenz 49

pancreatic lesions 143 papilloma virus vector, bovine 96 papovaviruses 176 paraffin embedding 196 parasite 234 particle-to-infectivity ratios 41 , 42 parvovirus 43 parvoviruses 200 passage 276 pathogenesis 219, 276 pathology 220 PC12 cells 98 PEG (polyethylene glycol) 46 peroxides 196 persistence of viral infections - Epstein-Barr virus 175, 176 - papovaviruses 176

284 Subject Index

phage - lambda 217 - fd 217 - PM2 217 phanerosis 279 phenolics 196 phosphatidylinositol (PI) 95, 98, 99, 104 - specific phospholipase C

(PIPLC) 98-104 phylogenetic tree 117, 118 physical particle 41 - viruses 41 Poisson distribution 198 poliovirus 43 porcine circovirus 199, 200 post-translational modifications 110 - prion proteins 241 potato X virus 204 prion(s) 233 -' (see also scrapie) - diseases - - genetic 234 - - infectious 234 - - sporadic 234 - hypothesis 136, 214, 221 - - paradox 203,205,209,213 - multiple forms 248 - - DLPCs 248 - - liposomes 248 - - rods 248 - protein (PrP) 75, 109, 128, 130, 135,

136,213,221 - - accumulation in brain 128, 130, 135,

136 - - allotypes, mice 159 - - alternative conformations 162 - - biosynthesis 93-107 - - - effect of scrapie in-

fection 101-104 - - cell surface receptor 221 - - function 219 - - gene(s) 109,237,243 - - - cell-free transcription and trans-

lation 94, 95 - - - conservation among species 116 - - - divergence 116 - - - expression 155 - - - hamster 94 - - - human 94 - - - linkage with scrapie incubation time

gene, mice 155-158 - - - linkage with human prion dis­

ease 158 - - - mapping, mouse 157 - - - mouse 94, 95

- - - mutations 120 - - - organization 240 - - - polymorphisms 219 - - - promoter 155 - - - rat 94 - - - relatedness 116 - - - sheep 94 - - - speciation of mammals 240 - - gene structure 59,240 - - - chromosomal location 60 - - - linkage to Sinc and other host in-

cubation time control genes 61, 67 - - - linkage to incidence of GSS,

CJD 61,67 - - glycosylation 98-100, 102 - - half life 100,103,104 - - in vitro expression 94-98 - - - baculovirus vector 97,98 - - - bovine papilloma virus vector 96 - - - C127 cells 95-98 - - - cell-free transcription and trans-

lation 94, 95 - - - COS-7 cells 97,98 - - - hamster cDNA 94,95,97,98 - - - mouse cDNA 95-97 - - - spodoptera cells 97,98 - - - SV40-based vector 97 - - infectivity, proportionality 215,217 - - isoforms 154 - - labeling - - - biotinylation 100, 103 - - - immunofluorescence 100, 101,

103 - - - (35S)-methionine 96, 98-101 - - - radioiodination 100 ' - - linkage with Sinc gene 136 - - membrane topology 95, 100, 101,

103,104 - - metabolism 162 - - mRNA - - - art2, Alu-like repeat sequences 60 - - - correlation with infectivity 63 - - - correlation with PrP im-

munohistochemistry 63, 64 - - - in brain 61-63 - - - in non-CNS tissues 63 - - - in situ hybridization 62, 63 - - - Northern blotting 60 - - - regulation of expression during

development 68 - - - S1-nuclease mapping 61 - - - size 60 - - - species variability 60 - - - 3'-untranslated region 60

- - N-terminal truncation 99, 101, 102 - - post-translational modifications 241 - - PK-resistant (Proteinase K-resistant) - - - biochemical analyses 182, 186,

191 - - - immunoblotting 188 - - polymorph isms 136 - - precursors 96, 98-100 - - protease resistantform 97,101-104 - - regulation of - - - susceptibility 221 - - - replication 221 - - stop transfer sequence 95, 103 - - structural aspects 119 - - - hydrophobic domain 120 - - subcellular localization 100-104 - rod(s) 47,79,82, 197 - - formation 82 - - morphology, variations 85-87 - - SAF 80 Prn-i 156, 237 Prn-p 156, 237 proportionality of PrP and infectivity 215,

217 protease 215 - resistant protein (PrP) 144-148 - - immune response 146 - - posttranslational rnodifications 148,

149 - sensitivity 147 - - strain differences 144,147 - - western plot profile 144, 147 proteinase 210 - K 182, 186, 188, 191 - - digestion 46-48 - - resistance 97 PrP (see also prion protein) 128, 130,

135,136,213,221 PrP-27-30 39,46,47,49,110,236,237 - disease specific protein 47 - natural disease 48 - precursor 48 - prion rods 47 - protein sequencing 48 - radiochemical labeling 46 - SAF 47 - scrapie agent component 47 PrPc (cellular isoform) - allelic variants 61,67 - - linkage to host incubation period con-

trol genes 61, 67 - glypiation 61, 64 - immunohistochemistry 61-63 - - in brain 61-63

Subject Index 285

- - in cell lines 63 - kinetics of biosynthesis 65 - - half-life 65 - - multiple forms 65 - - neuroblastom cells 65 - monomer or oligomer 67 - - insight form genetics 67 - - PrP ligands 67 - physiological function 67 - - cell adhesion molecule 68 - - GFAP-stimulating factor 68 - - lymphocyte-activation signal 68 - post-translational modification 61 - - glycosylation 61 - - plasma membrane attachment 64 - purification 64 - - affinity chromatography 64 - - contaminating proteins 64 - - yield 64 - topography 65 - - chaperones 67 - - domain structure 66 - - membrane orienta-

tion/translocation 66 - - predicted structure 66 - - SP6-transcription/translation 66 - - stop-transfer effector sequence 66 PrPSc 39, 236, 237 - biochemical purification 236 - Golgi apparatus 238 - immunoaffinity purification 236 - neutralization 236 - purification with scrapie agent 48 purification 213

quaternary amines 196

radiation - ionizing 196 - - inactivation rate constant 196-198 - - target size 196-203 - ultraviolet 204 - - inactivation spectrum 204 radiobiological investigations 246 replication 211 - agent 219 - - in vitro, CJD 190 - regulation of PrP 221 retroviruses 43 RFLP, PrP gene 173,174 rida (see also scrapie) 168,169 rods 75

286 Subject Index

SAF (scrapie associated fibrils) 27, 47-49,70,80,144,148,197

- CJD-affected brains 47 - infectivity 58 - - PrP monomers 59, 67 - - PrP oligomers 59, 67 - - ScPrP 68 - protein 39,47 - - composition 47 - purification 47 - scrapie isoform 58 Scottish blackface experiment 167 scrapie 1, 75, 139, 149 - agent - - biological properties 41 - - cell interactions - - - hamster glioma cells 185 - - - hamster neuroblasoma cells 185 - - - hybridoma cultures 183, 186 - - - morphological characteristics 182,

189,190 - - - splenotropic neoplastic cell

lines 182 - - characterization of purified frac-

tions 45 - - definition 41 , 42 - - density 40 - - mitoplast fractions 49 - - physical particle 41 - - - definition 42 - - properties 40 - - SAF 47 - - separation from Sp33-37 49 - - size 39 - - structural hypothesis 52 - - titers - - - bioassay of cultured cells 187,

188 - - - comparison with mouse tis-

sues 190 - - - frequency of infected cells 186 - - - limited dilution cloning 186 - clinical signs 24, 25 - fibrils, associated see SAF - historical 21, 22 - Icelandic scrapie (rida) 168, 169 - informational molecule 133,135,136 - - mutation 133-135 - isoform, ScPrP - - association with infectivity 69 - - effect of agent strain and Sinc

genotype 69 - - - and vacuolation 69 - - - and amyloidosis 69

- - immunohistochemistry 68-70 - - kinetics of biosynthesis 70 - - - half-life 70 - - - immunogold electron micro-

scopy 70 - - - intracellular accumulation 70 - - - neuroblastom cells 70 - - - secondary Iysosomes 70 - - SAF 58 - isolates 125-136, 158, 159, 161, 162 - - Chandler 134 - - drowsy goat 125,131 - - scratching goat 125, 131 - natural 233 - - age 166 - - familial incidence 166, 167 - - Icelandic scrapie (rida) 168, 169 - neuropathology 26, 27 - possible source of BSE 33 - route of exposure 31 - specific nucleic acid 161,162,245, 247 - strain(s) 125-136,247 - - 22A 127,134 - - 22C 132,133 - - 22F 134 - - 22H 131 - - 22L 127,128 - - 79A 131 - - 79V 131 - - 87A 132-134 - - 87V 69,128-130, 132 - - 139A ("Chandler") 134 - - 263K 69 - - biological characteristics 140-143 - - - amyloid 140 - - - glucose tolerance 142 - - - histopathology 142, 143 - - - host-agent infuences 141-144 - - - incubation period 140, 141, 143,

146 - - - insulin levels 143 - - - pancreatic lesions 143 - - - vacuolation 140, 142 - - - weight changes 140, 141, 142 - - biological cloning 132, 133 - - comparison among 142-144,147 - - discrimination 125-130 - - - brain pathology 127-130 - - - incubation periods 126, 127 - - Fukuoka-1 strain of CJD 69 - - hamster adapted 139, 141, 143, 146 - - implications 135, 136 - - interactions with Sinc gene 126,

127,136

- - isolation 130-132 - - ME7 59,69,128-130,132-134 - - mouse adapted 139-142,147 - - selection 131-135 - - - from mixtures 133, 134 - - - of mutants 131-134 - - stability of properties 133, 134 - - variation 196 screening, differential 211, 261-263, 265 sedimentation 215 - velocity 204,206,214 Sinc 155, 156 - gene 126,127,130,131,136 - - control of incubation period 126,

127,136 - - interactions with scrapie strains 126,

127, 136 - - linkage with PrP gene 136 - - s7 and p7 alleles 126 - genotype 148 Sip gene, Cheviot sheep 170-174 sonication 203 Sp1 111 Sp33-37 39,49,51 - natural disease 48 - precursor to PrP-27-30 48 - protein sequencing 48 - purification with scrapie agent 48 species barrier 134, 135, 143, 146,

149 - scrapie strain selection 135 - to scrapie transmission 158-161 species tropism - mouse derived scrapie agent 185 - hamster derived scrapie agent 185 specific - activity 42, 43 - - parvovirus 43 - - poliovirus 43 - - retroviruses 43 - - scrapie agent 43,46-49,51 - infectivity 210, 214, 221 splenotropic neoplastic cell lines 182 spodoptera cells 97, 98 spongiform encephalopathy (see also en-

cephalopathy) 276 spontanous de novo transformation 3 stereotaxic inoculation 142, 143 sterilization 208 strain variation 211, 213 - 22A strain 212 - 263K strain 212 - ME7 strain 212 street rabies virus 175

Subject Index 287

structural parameters 144-148 - host agent infuencies 145, 146, 148 subacute spongiform virus en-

cephalopathies 1 subtractive hybridization 211 subviral size 197 susceptibility - biochemical markers - - OlA haplotypes 173 - - PrP gene RFlPs 173, 174 - familial CJD 219 - genetic control - - scrapie 170-174 - - - Cheviot sheep 170-174 - - - Herwick sheep 171, 173 - - - Swaledale sheep 171, 172 - - other diseases - - - mouse hepatitis virus 175 - - - mouse pox 174 - - - street rabies virus 175 - Gerstmann-Straussler syndrome

(GSS) 219 - regulation, PrP 221 SV40-based vector 97

target size(s) 196-203,247 TATA box 111 tissue cultures supporting scrapie agent - C-1300 cells 184 - explant cultures 182, 183, 185, 190 - mouse l fibroblasts 184, 185 - N2a cells 184, 190, 191 -NIE-115cells 184 - PC-12 cells 184,186,187,191 - 5MB cultures 181,182 titers of Phi x 174 217 tobacco mosaic virus 204, 206 transgenic 220 - mice 159-161,219,238 transmissible - agent 275 - mink encephalopathy - - historical 22 - - route of exposure 31 - spongiform encephalopathy,

origins 14, 15 transmission - interspecies 130-132, 134, 135 - maternal - - Scottish blackface experiment 167 - - Mission Texas experiment 167,168 - natural - - contagion 167,168 - pasture contamination 169

288 Subject Index

transmission - route of infection 168, 169 - scrapie 158-161 - viremia 276 trypsin digestion 48 tunicamycin 98

ultrasonication 217,218 ultrastructural investigations 77 - fibrils 77 - filaments 77 - rods 77 - tubules 77 - vesicles 77 ultraviolet irradiation 245 unconventional - virus 234

viral 275 - capsid 210 - infections, persistence - - Epstein-Barr virus 175, 176 - - papovaviruses 176

viremia 276 - hamsters 276 - transmission 276 virino 234 - hypothesis 52, 136 virions 2 viroid 206 virucidal treatments 196 virus(es) 234, 249 - case for 195 - definition 197 - hypothesis 52 - nucleic acid molecular weight 198

western blot 144,147

Xenopus oocytes 97

yellow fever virus 201 yield 44 - scrapie agent 46-48

Zn2+ hydrolysis 211

Current Topics in Microbiology and Immunology

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