B19, see Parvovirus B19 Bone marrow, gene transfer with parvovirus. Erythrovirus, see Parvovirus B19, Simian parvovirus

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1 ... Subject Index Adeno-associated virus Cap and genome encapsidation 87 DNA integration homologous recombination 90, 91 latency vs replication 77, 78 mechanism 79 requirements 78, 79 site in human genome 68, 78, 87, 89, 90 transcriptional activity at integration site 79, 80 DNA replication cell cycle 74 cell-free system development 74 helper factors 76, 77, 89 mechanism 75±77 persistence 89, 90 rates 74 entry mechanisms 88, 89 epidemiology 59 gene transfer, see Gene transfer, adenoassociated virus genome features 70, 71, 87 helper viruses 60, 68, 72±74 latency 68, 71, 77, 78, 86 oncosuppression 60 particle features 69, 87 pathogenicity 59, 62, 78 receptors 88 serotypes 60 sexual transmission 61 tissue distribution female reproductive tract 61, 62 hear 62 lung 62 transcriptional regulation E protein roles 73 PC4 role 72 Rep role 71, 72, 87 Sp1 role 73 Aedes aegypti densovirus, see Densovirus, Aleutian mink disease parvovirus clinical manifestations 154, 155 hosts 156 immune response 155, 156 pathogenesis 155 persistence 150 prevention of infection 156, 157 target cells 155 Autonomous, see also specific viruses cell entry 165 gene transfer, see Gene transfer, autonomous molecular biology, see Minute virus of 204

2 mice, Rodent stability 164, 180 structure 164±166, 181, 184 Autosomal retinitis pigmentosa, gene therapy with adeno-associated virus vector 102 B19, see Parvovirus B19 Bone marrow, gene transfer with parvovirus B19 141, 142 Canine parvovirus epidemiology 152 feline panleukopenia virus homology 150, 151 hosts 150 neonatal infection 153, 154 pathogenesis 152, 153 stability 164 tissue specificity 152 vaccination 154 Cystic fibrosis, gene therapy with adenoassociated virus vector 86, 100, 101 Densovirus biophysical properties of virions 15, 16 classification and taxonomy 1, 13±15 epidemiology epizootiology in insect populations 7 host range 5, 6, 12, 34 Galleria mellonella densovirus structure capsid protein 18 protein-dna interactions 19 VP proteins 17±19 genome organization 19, 21, 34, 35, 37 polyamine association 17 replication models 24, 25, 27, 30 self-priming hairpins 27 size 16 terminal repeats 16, 25 geographic distribution 1, 3 histopathology 4 insect pest control 8, 9, 30, 33, 34 NS1 role in replication 27±30, 34 sequence homology with vertebrate parvovirus NS and VP proteins 23, 24 structural proteins 17 symptoms of infection 3, 4 transcription 21±23 translation 22, 23 ultrastructure of infected cells 4, 5 Dependovirus, see Adeno-associated virus Erythrovirus, see Parvovirus B19, Simian parvovirus Factor IX, gene therapy with adeno-associated virus vector 100±102 Feline panleukopenia virus canine parvovirus homology 150, 151 epidemiology 152 hosts 150 neonatal infection 153, 154 pathogenesis 152, 153 tissue specificity 152 vaccination 154 Galleria mellonella densovirus, see Densovirus, Gene transfer, adeno-associated virus hybrid type I vectors autonomous replication 135, 136 erythroid cell specificity 135, 136, 138, 140 overview 134, 135 promoter analysis 136, 138, 140 hybrid type II vectors erythroid progenitor targeting in bone marrow 141, 142 overview 140, 141 advantages 85, 86, 134 applications and clinical trials autosomal retinitis pigmentosa prospects 102 cystic fibrosis 86, 100, 101 hemophilia B and factor IX 100±102 cell culture transduction 95, 96 Subject Index 205

3 cell targeting 96, 97 design of vectors 91 expression levels 97, 98 immune response 98, 99 persistence of expression 97, 98 tissue specificity 86 toxicity 99 vector production complementation systems 92±94 overview 91, 92 purification 95 replication-competent vectors 94, 95 wild-type virus 94, 95 Gene transfer, autonomous advantages and disadvantages 180, 181 applications 179, 180 limitations and prospects 197, 198 safety 180 vector design with rodent capsid replacement in minute virus of mice chloramphenicol acetyltransferase transduction 192, 193 interleukin insertion 191, 192 replication-competent virus interference and suppression 193±197 complete coding replacement in parvovirus Lu III 190, 191 general considerations 188±190 H1-based vectors 194 promoter replacement 197 advantages of system 55, 56 clone infectivity 37, 38 expression systems Aedes aegypti densovirus 40±43 chloramphenicol acetyltransferase expression 40 fusion protein expression 41, 42 b-galactosidase expression 39±41 Galleria mellonella densovirus 40 green fluorescent protein expression 42, 43, 49 GUS expression 41 Junonia coenia densovirus 39, 40 promoter strength 38 VP fusion protein expression 43 long-term expression 54, 55 transducing vectors Aedes aegypti densovirus 46, 47, 52, 53 helper plasmids 43±45, 48, 49 Junonia coenia densovirus 45, 46 mosquito larva transduction with Aedes aegypti densovirus 52, 53, 55 overview 43±45 Sindbis virus helper 51, 52 transformation of cells with VP and NS genes 49±51 Gene transfer, parvovirus B19 hybrid type I vectors autonomous replication 135, 136 erythroid cell specificity 135, 136, 138, 140 overview 134, 135 promoter analysis 136, 138, 140 hybrid type II vectors erythroid progenitor targeting in bone marrow 141, 142 overview 140, 141 Goose parvovirus, overview 160 H-1 virus, see Gene transfer, autonomous Hamster parvovirus, overview 158, 159 Hemophilia B, gene therapy with adenoassociated virus vector 100±102 Insects densovirus epizootiology 7 mosquito larva transduction with Aedes aegypti densovirus 52, 53, 55 pest control 8, 9, 30, 33, 34 gene transfer, see Junonia coenia densovirus, see Densovirus, Subject Index 206

4 Killham rat virus, overview 158, 159 LuIII, see Gene transfer, autonomous Minute virus of canines, overview 160 Minute virus of mice DNA replication Cavalier-Smith model 171±173 NS1 role 174, 175 replicative form of DNA 171, 173, 174 single-stranded DNA synthesis 174, 175 gene transfer, see Gene transfer, autonomous genome organization 166, 167 life cycle 175, 176 overview 158, 159, 164 stability 180 transcription control 169±171 E2F role 169 NS1 role 169, 171 promoters 167±171 RNA splicing 169, 170 template 166 termination 167, 168 Mosquito, see Insects Mouse parvovirus, overview 158, 159 NS1 densovirus replication role 27±30, 34 transformation of cells with genes 49±51 minute virus of mice replication role 174, 175 transcription role 169, 171 parvovirus B19 replication role 126, 127 transcription role 127 cytotoxicity 127 rodent parvovirus replication role 183, 184 NS2, rodent parvovirus replication role 183 Parvovirus B19 capsid protein functions 128, 129 cell culture infection and propagation 110, 111 cellular tropism 124, 125, 133, 134 clinical manifestations of infection erythema infectiosum 115 immunocompromised patients 117 myocarditis 118 overview 108, 115 pregnancy 117, 118 thrombocytopenia 118 transient aplastic crisis 115, 117 vasculitis 118 cytotoxicity 111 epidemic behavior and contagiousness 109 experimental infection and host response 112±114 genetic restriction to infection 123, 124 gene transfer, see Gene transfer, parvovirus B19 genome organization 125, 126 homologous erythrovirus 123 immune response 128, 129 incidence of infection 108, 109 NS1 replication role 126, 127 transcription role 127 cytotoxicity 127 prevalence of infection 107, 108 receptor and cell entry 107, 112, 124, 128, 134 transcription 126 transmission 109, 110 Porcine parvovirus clinical manifestations 157 isolates 157 stability and persistence 158 vaccination 158 Rat parvovirus type 1, overview 158, 159 Rodent, see also specific viruses encapsidation 182 epidemiology 159 Subject Index 207

5 gene transfer, see Gene transfer, autonomous genome efficiency of usage 184 organization 182 hamster parvovirus 158, 159 Killham rat virus 158, 159 minute virus of mice 158, 159, 164 mouse parvovirus 158, 159 rat parvovirus type 1 158, 159 replication NS1 role 183, 184 NS2 role 183 transcription 183 types 158 Simian parvovirus cell culture infection and propagation 111 epidemic behavior and contagiousness 109 experimental infection and host response 114 prevalence of infection 108 transmission 110 types 107 Transduction, see Gene transfer Transmission adeno-associated virus 61 canine parvovirus 152 densovirus 7 feline panleukopenia virus 152 parvovirus B19 109, 110 rodent 159 simian parvovirus 110 VP proteins, densovirus fusion protein expression 43 transformation of cells with genes 49±51 types 17±19 Subject Index 208