JP6772155B2 - エンテロウイルス71動物モデル - Google Patents
エンテロウイルス71動物モデル Download PDFInfo
- Publication number
- JP6772155B2 JP6772155B2 JP2017540259A JP2017540259A JP6772155B2 JP 6772155 B2 JP6772155 B2 JP 6772155B2 JP 2017540259 A JP2017540259 A JP 2017540259A JP 2017540259 A JP2017540259 A JP 2017540259A JP 6772155 B2 JP6772155 B2 JP 6772155B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- mouse
- infected
- virus
- mice
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241001529459 Enterovirus A71 Species 0.000 title claims description 564
- 238000010171 animal model Methods 0.000 title claims description 72
- 208000015181 infectious disease Diseases 0.000 claims description 142
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 140
- 241000699670 Mus sp. Species 0.000 claims description 130
- 241001465754 Metazoa Species 0.000 claims description 115
- 238000000034 method Methods 0.000 claims description 76
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 58
- 201000010099 disease Diseases 0.000 claims description 55
- 238000012360 testing method Methods 0.000 claims description 48
- 210000001519 tissue Anatomy 0.000 claims description 44
- 210000002966 serum Anatomy 0.000 claims description 35
- 206010061818 Disease progression Diseases 0.000 claims description 33
- 230000005750 disease progression Effects 0.000 claims description 33
- 238000012216 screening Methods 0.000 claims description 32
- 108020000999 Viral RNA Proteins 0.000 claims description 29
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 23
- 208000005333 pulmonary edema Diseases 0.000 claims description 23
- 239000003443 antiviral agent Substances 0.000 claims description 21
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 claims description 17
- 229960004854 viral vaccine Drugs 0.000 claims description 17
- 230000001272 neurogenic effect Effects 0.000 claims description 15
- 230000002829 reductive effect Effects 0.000 claims description 14
- 210000000133 brain stem Anatomy 0.000 claims description 13
- 150000003943 catecholamines Chemical class 0.000 claims description 13
- 208000024891 symptom Diseases 0.000 claims description 13
- 230000001154 acute effect Effects 0.000 claims description 12
- 238000004113 cell culture Methods 0.000 claims description 12
- 230000001537 neural effect Effects 0.000 claims description 10
- 208000032843 Hemorrhage Diseases 0.000 claims description 8
- 229940000406 drug candidate Drugs 0.000 claims description 8
- 230000002441 reversible effect Effects 0.000 claims description 8
- 201000002491 encephalomyelitis Diseases 0.000 claims description 6
- 230000001524 infective effect Effects 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 210000003205 muscle Anatomy 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 239000007928 intraperitoneal injection Substances 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 claims 2
- 210000004027 cell Anatomy 0.000 description 431
- 241000700605 Viruses Species 0.000 description 188
- 230000003612 virological effect Effects 0.000 description 142
- 241000283984 Rodentia Species 0.000 description 141
- 230000035772 mutation Effects 0.000 description 79
- 239000000427 antigen Substances 0.000 description 76
- 108091007433 antigens Proteins 0.000 description 76
- 102000036639 antigens Human genes 0.000 description 76
- 230000000120 cytopathologic effect Effects 0.000 description 73
- 210000003501 vero cell Anatomy 0.000 description 57
- 108090000623 proteins and genes Proteins 0.000 description 55
- 102000004169 proteins and genes Human genes 0.000 description 50
- 238000006467 substitution reaction Methods 0.000 description 44
- 125000003275 alpha amino acid group Chemical group 0.000 description 38
- 241001529936 Murinae Species 0.000 description 37
- 102200135781 rs1042140 Human genes 0.000 description 32
- 230000003902 lesion Effects 0.000 description 30
- 210000004072 lung Anatomy 0.000 description 30
- 239000006228 supernatant Substances 0.000 description 29
- 210000000234 capsid Anatomy 0.000 description 27
- 238000001890 transfection Methods 0.000 description 21
- 239000002299 complementary DNA Substances 0.000 description 20
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 19
- 241000283973 Oryctolagus cuniculus Species 0.000 description 19
- 241000288906 Primates Species 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 19
- 108020003175 receptors Proteins 0.000 description 19
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 18
- 238000001514 detection method Methods 0.000 description 18
- 230000002062 proliferating effect Effects 0.000 description 18
- 101000716481 Homo sapiens Lysosome membrane protein 2 Proteins 0.000 description 17
- 210000004556 brain Anatomy 0.000 description 17
- 102000045687 human SCARB2 Human genes 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 16
- 208000012902 Nervous system disease Diseases 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 239000012228 culture supernatant Substances 0.000 description 15
- 239000012634 fragment Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 206010033799 Paralysis Diseases 0.000 description 14
- 150000001413 amino acids Chemical class 0.000 description 14
- 230000007170 pathology Effects 0.000 description 14
- 238000001228 spectrum Methods 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 13
- 238000011081 inoculation Methods 0.000 description 13
- 238000007912 intraperitoneal administration Methods 0.000 description 13
- 230000010076 replication Effects 0.000 description 13
- 108090000565 Capsid Proteins Proteins 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 238000007918 intramuscular administration Methods 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 102100023321 Ceruloplasmin Human genes 0.000 description 11
- 208000025966 Neurological disease Diseases 0.000 description 11
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 238000009826 distribution Methods 0.000 description 11
- 230000006698 induction Effects 0.000 description 11
- 210000002569 neuron Anatomy 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- 241000306271 Colombian datura virus Species 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 238000011533 pre-incubation Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000004809 Teflon Substances 0.000 description 9
- 229920006362 Teflon® Polymers 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 210000002950 fibroblast Anatomy 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- 230000002458 infectious effect Effects 0.000 description 9
- 231100000518 lethal Toxicity 0.000 description 9
- 230000001665 lethal effect Effects 0.000 description 9
- 210000003141 lower extremity Anatomy 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- 230000029812 viral genome replication Effects 0.000 description 9
- 206010013975 Dyspnoeas Diseases 0.000 description 8
- 101100095199 Mus musculus Scarb2 gene Proteins 0.000 description 8
- 206010044565 Tremor Diseases 0.000 description 8
- 230000034994 death Effects 0.000 description 8
- 231100000517 death Toxicity 0.000 description 8
- 238000010166 immunofluorescence Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000003472 neutralizing effect Effects 0.000 description 8
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 7
- 208000000059 Dyspnea Diseases 0.000 description 7
- 208000020061 Hand, Foot and Mouth Disease Diseases 0.000 description 7
- 208000025713 Hand-foot-and-mouth disease Diseases 0.000 description 7
- 208000036142 Viral infection Diseases 0.000 description 7
- 230000006978 adaptation Effects 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000000740 bleeding effect Effects 0.000 description 7
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 210000001767 medulla oblongata Anatomy 0.000 description 7
- 210000001259 mesencephalon Anatomy 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000009385 viral infection Effects 0.000 description 7
- 241000282693 Cercopithecidae Species 0.000 description 6
- 206010010071 Coma Diseases 0.000 description 6
- 206010015548 Euthanasia Diseases 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 6
- 238000011888 autopsy Methods 0.000 description 6
- 239000013553 cell monolayer Substances 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000009368 gene silencing by RNA Effects 0.000 description 6
- 210000005003 heart tissue Anatomy 0.000 description 6
- 210000001320 hippocampus Anatomy 0.000 description 6
- 210000003016 hypothalamus Anatomy 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 230000002101 lytic effect Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 230000000241 respiratory effect Effects 0.000 description 6
- 210000000278 spinal cord Anatomy 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 108020003589 5' Untranslated Regions Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 206010061598 Immunodeficiency Diseases 0.000 description 5
- 108010054395 P-selectin ligand protein Proteins 0.000 description 5
- 108010076039 Polyproteins Proteins 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000003198 cerebellar cortex Anatomy 0.000 description 5
- 210000001638 cerebellum Anatomy 0.000 description 5
- 210000003414 extremity Anatomy 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000004807 localization Effects 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 210000001103 thalamus Anatomy 0.000 description 5
- 230000000451 tissue damage Effects 0.000 description 5
- 231100000827 tissue damage Toxicity 0.000 description 5
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- 102100020983 Lysosome membrane protein 2 Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 108060004795 Methyltransferase Proteins 0.000 description 4
- 206010028851 Necrosis Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 108091005488 SCARB2 Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 206010069555 Use of accessory respiratory muscles Diseases 0.000 description 4
- 108010067390 Viral Proteins Proteins 0.000 description 4
- 108070000030 Viral receptors Proteins 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 210000005013 brain tissue Anatomy 0.000 description 4
- 238000012754 cardiac puncture Methods 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 229960002748 norepinephrine Drugs 0.000 description 4
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 230000002085 persistent effect Effects 0.000 description 4
- 238000013207 serial dilution Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- 108020005345 3' Untranslated Regions Proteins 0.000 description 3
- 206010003591 Ataxia Diseases 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- 239000012097 Lipofectamine 2000 Substances 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 206010029260 Neuroblastoma Diseases 0.000 description 3
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000003591 cerebellar nuclei Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 230000001461 cytolytic effect Effects 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 229960003964 deoxycholic acid Drugs 0.000 description 3
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 241001493065 dsRNA viruses Species 0.000 description 3
- 206010014599 encephalitis Diseases 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 231100000225 lethality Toxicity 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 210000000337 motor cortex Anatomy 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 230000007918 pathogenicity Effects 0.000 description 3
- 210000002509 periaqueductal gray Anatomy 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 208000008203 tachypnea Diseases 0.000 description 3
- 206010043089 tachypnoea Diseases 0.000 description 3
- 210000003813 thumb Anatomy 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 239000003656 tris buffered saline Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- 206010003840 Autonomic nervous system imbalance Diseases 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 241000282552 Chlorocebus aethiops Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 241000988559 Enterovirus A Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010029660 Intrinsically Disordered Proteins Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 206010051295 Neurological infection Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000033952 Paralysis flaccid Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 208000010513 Stupor Diseases 0.000 description 2
- 108010087302 Viral Structural Proteins Proteins 0.000 description 2
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000002155 anti-virotic effect Effects 0.000 description 2
- 238000013475 authorization Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000001269 cardiogenic effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 210000002451 diencephalon Anatomy 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000834 fixative Substances 0.000 description 2
- 208000028331 flaccid paralysis Diseases 0.000 description 2
- 210000004884 grey matter Anatomy 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003447 ipsilateral effect Effects 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 238000001325 log-rank test Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000003032 molecular docking Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 210000002975 pon Anatomy 0.000 description 2
- 210000001176 projection neuron Anatomy 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000004189 reticular formation Anatomy 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000001679 solitary nucleus Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 210000003371 toe Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000014599 transmission of virus Effects 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 238000003260 vortexing Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 208000006740 Aseptic Meningitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- 108091033409 CRISPR Proteins 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 101710197658 Capsid protein VP1 Proteins 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 206010067671 Disease complication Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 101710121996 Hexon protein p72 Proteins 0.000 description 1
- 208000031361 Hiccup Diseases 0.000 description 1
- 101001113490 Homo sapiens Poly(A)-specific ribonuclease PARN Proteins 0.000 description 1
- 241001207270 Human enterovirus Species 0.000 description 1
- 102000001617 Interferon Receptors Human genes 0.000 description 1
- 108010054267 Interferon Receptors Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 206010027201 Meningitis aseptic Diseases 0.000 description 1
- 206010027925 Monoparesis Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 108010094052 Nik related kinase Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 102100023715 Poly(A)-specific ribonuclease PARN Human genes 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 206010037394 Pulmonary haemorrhage Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 108010067674 Viral Nonstructural Proteins Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 206010052015 cytokine release syndrome Diseases 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000010460 detection of virus Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000026502 entry into host cell Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 210000003811 finger Anatomy 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000012750 in vivo screening Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000010983 kinetics study Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000005230 lumbar spinal cord Anatomy 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 210000001073 mediodorsal thalamic nucleus Anatomy 0.000 description 1
- 238000002941 microtiter virus yield reduction assay Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 244000309711 non-enveloped viruses Species 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 208000025223 poliovirus infection Diseases 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000004088 pulmonary circulation Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000008695 pulmonary vasoconstriction Effects 0.000 description 1
- 210000000449 purkinje cell Anatomy 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000013643 reference control Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 108091005484 scavenger receptor class B Proteins 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 210000004092 somatosensory cortex Anatomy 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000003863 superior colliculi Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 210000003901 trigeminal nerve Anatomy 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 230000007502 viral entry Effects 0.000 description 1
- 230000007485 viral shedding Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000005723 virus inoculator Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0337—Animal models for infectious diseases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32311—Enterovirus
- C12N2770/32321—Viruses as such, e.g. new isolates, mutants or their genomic sequences
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32311—Enterovirus
- C12N2770/32322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32311—Enterovirus
- C12N2770/32371—Demonstrated in vivo effect
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Environmental Sciences (AREA)
- Cell Biology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- General Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Rheumatology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562108828P | 2015-01-28 | 2015-01-28 | |
US62/108,828 | 2015-01-28 | ||
US201562114880P | 2015-02-11 | 2015-02-11 | |
US62/114,880 | 2015-02-11 | ||
PCT/SG2016/050031 WO2016122403A1 (en) | 2015-01-28 | 2016-01-25 | Enterovirus 71 animal model |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018513671A JP2018513671A (ja) | 2018-05-31 |
JP2018513671A5 JP2018513671A5 (zh) | 2020-04-16 |
JP6772155B2 true JP6772155B2 (ja) | 2020-10-21 |
Family
ID=56543857
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017540259A Active JP6772155B2 (ja) | 2015-01-28 | 2016-01-25 | エンテロウイルス71動物モデル |
Country Status (8)
Country | Link |
---|---|
JP (1) | JP6772155B2 (zh) |
KR (1) | KR20170106473A (zh) |
CN (1) | CN107849540B (zh) |
AU (1) | AU2016212766B2 (zh) |
MY (1) | MY202113A (zh) |
SG (1) | SG11201706054QA (zh) |
TW (1) | TWI764859B (zh) |
WO (1) | WO2016122403A1 (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112094822A (zh) * | 2019-06-02 | 2020-12-18 | 复旦大学 | 基于EV71毒株的感染性cDNA克隆及其应用 |
KR102243526B1 (ko) * | 2020-01-21 | 2021-04-22 | (주)노터스생명과학 | 수족구백신의 비임상 평가용 형질전환 동물 및 이의 제조방법 |
US20240043944A1 (en) * | 2020-12-21 | 2024-02-08 | Chiaho Shih | Novel enterovirus 71 mutations associated with disease severity |
CN114304064A (zh) * | 2021-12-16 | 2022-04-12 | 首都医科大学 | 一种头部畸形伴神经-运动障碍动物模型的建立方法 |
CN115211402A (zh) * | 2022-07-07 | 2022-10-21 | 中国医学科学院医学生物学研究所 | 一种cv-b3感染的啮齿动物模型的构建方法和用途 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102220288B (zh) * | 2011-05-04 | 2013-07-17 | 中国科学院上海巴斯德研究所 | 一种肠道病毒ev71型鼠适应株573及其应用 |
-
2016
- 2016-01-25 AU AU2016212766A patent/AU2016212766B2/en active Active
- 2016-01-25 SG SG11201706054QA patent/SG11201706054QA/en unknown
- 2016-01-25 CN CN201680019293.5A patent/CN107849540B/zh active Active
- 2016-01-25 WO PCT/SG2016/050031 patent/WO2016122403A1/en active Application Filing
- 2016-01-25 MY MYPI2017001107A patent/MY202113A/en unknown
- 2016-01-25 JP JP2017540259A patent/JP6772155B2/ja active Active
- 2016-01-25 KR KR1020177023889A patent/KR20170106473A/ko not_active Application Discontinuation
- 2016-01-27 TW TW105102566A patent/TWI764859B/zh active
Also Published As
Publication number | Publication date |
---|---|
WO2016122403A1 (en) | 2016-08-04 |
TWI764859B (zh) | 2022-05-21 |
AU2016212766A1 (en) | 2017-09-07 |
MY202113A (en) | 2024-04-04 |
AU2016212766B2 (en) | 2022-03-24 |
SG11201706054QA (en) | 2017-08-30 |
KR20170106473A (ko) | 2017-09-20 |
JP2018513671A (ja) | 2018-05-31 |
TW201702376A (zh) | 2017-01-16 |
CN107849540B (zh) | 2021-12-21 |
CN107849540A (zh) | 2018-03-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6772155B2 (ja) | エンテロウイルス71動物モデル | |
Wang et al. | Adaptation of African swine fever virus to HEK293T cells | |
Wickramasinghe et al. | The avian coronavirus spike protein | |
KR101243871B1 (ko) | 개 파보바이러스의 유전자 변이체를 포함하는 백신 | |
Jager et al. | Small but mighty: old and new parvoviruses of veterinary significance | |
Caldera-Crespo et al. | Experimental models of COVID-19 | |
Huang et al. | Molecular characterization of the small nonstructural proteins of parvovirus Aleutian mink disease virus (AMDV) during infection | |
Shao et al. | Antibodies against outer-capsid proteins of grass carp reovirus expressed in E. coli are capable of neutralizing viral infectivity | |
CN116802193A (zh) | 经改造冠状病毒刺突(s)蛋白及其使用方法 | |
Tamura et al. | Virological characteristics of the SARS-CoV-2 Omicron XBB. 1.5 variant | |
Tee et al. | Electrostatic interactions at the five-fold axis alter heparin-binding phenotype and drive enterovirus A71 virulence in mice | |
Van Gennip et al. | Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus | |
Kim et al. | Pathogenicity of porcine G9P [23] and G9P [7] rotaviruses in piglets | |
Victorio et al. | Cooperative effect of the VP1 amino acids 98E, 145A and 169F in the productive infection of mouse cell lines by enterovirus 71 (BS strain) | |
Busi et al. | Group A rotavirus associated with encephalitis in red fox | |
Yin et al. | Isolation and characterization of a novel chicken astrovirus in China | |
Cifuente et al. | Molecular determinants of disease in coxsackievirus B1 murine infection | |
Castellanos et al. | A slender tract of glycine residues is required for translocation of the VP2 protein N-terminal domain through the parvovirus MVM capsid channel to initiate infection | |
Gambhira et al. | Role of L2 cysteines in papillomavirus infection and neutralization | |
Yadav et al. | Rat hepatitis E virus (HEV) cross-species infection and transmission in pigs | |
Pranoto et al. | Porcine Circovirus Type 3: Diagnostics, Genotyping, and Challenges in Vaccine Development | |
Wang et al. | Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract | |
Kim et al. | A mouse xenograft long‐term replication yields a SARS‐CoV‐2 Delta mutant with increased lethality | |
Kailasan | Structure-function characterization of bocaparvoviruses | |
Mosley et al. | Infectious bursal disease virus as a replication-incompetent viral vector expressing green fluorescent protein |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190123 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200225 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20200225 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200528 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200828 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200911 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200930 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6772155 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |