Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice.
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Brain
/ immunology
COVID-19
/ immunology
Cytokine Release Syndrome
/ immunology
Disease Models, Animal
Disease Susceptibility
Genetic Predisposition to Disease
Keratin-18
/ genetics
Lung
/ immunology
Mice
Mice, Transgenic
Mortality
Promoter Regions, Genetic
/ genetics
Respiratory Mucosa
/ immunology
Virus Diseases
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 11 2020
30 11 2020
Historique:
received:
18
07
2020
accepted:
05
11
2020
entrez:
1
12
2020
pubmed:
2
12
2020
medline:
19
12
2020
Statut:
epublish
Résumé
Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.
Identifiants
pubmed: 33257679
doi: 10.1038/s41467-020-19891-7
pii: 10.1038/s41467-020-19891-7
pmc: PMC7705712
doi:
Substances chimiques
KRT18 protein, human
0
Keratin-18
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6122Références
Am J Trop Med Hyg. 2020 Sep;103(3):1215-1219
pubmed: 32723427
Front Immunol. 2018 Jun 07;9:888
pubmed: 29930549
Nature. 2020 May;581(7807):221-224
pubmed: 32225175
J Virol. 2007 Jan;81(2):813-21
pubmed: 17079315
Crit Rev Immunol. 2001;21(5):427-49
pubmed: 11942558
Annu Rev Immunol. 2015;33:417-43
pubmed: 25861977
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
J Virol. 2007 Aug;81(16):8692-706
pubmed: 17537853
Antiviral Res. 2013 Sep;99(3):230-7
pubmed: 23721943
Am J Respir Crit Care Med. 2020 May 15;201(10):1299-1300
pubmed: 32228035
Lancet. 2020 Feb 22;395(10224):565-574
pubmed: 32007145
Clin Microbiol Infect. 2020 Jun;26(6):767-772
pubmed: 32304745
Emerg Microbes Infect. 2020 Dec;9(1):2433-2445
pubmed: 33073694
Circ Res. 2020 May 8;126(10):1456-1474
pubmed: 32264791
J Med Virol. 2005 Feb;75(2):185-94
pubmed: 15602737
Clin Chim Acta. 2020 Oct;509:280-287
pubmed: 32531256
Int J Clin Exp Med. 2014 Sep 15;7(9):2718-23
pubmed: 25356130
J Immunol. 2014 Jul 1;193(1):285-94
pubmed: 24890725
Genome Med. 2020 Jul 28;12(1):68
pubmed: 32723359
Trends Immunol. 2016 Mar;37(3):181-192
pubmed: 26877243
J Immunol. 2012 Nov 1;189(9):4213-9
pubmed: 23087426
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
J Allergy Clin Immunol. 2020 Jul;146(1):110-118
pubmed: 32294485
Crit Care. 2020 Apr 16;24(1):154
pubmed: 32299472
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Cell. 2020 Aug 6;182(3):744-753.e4
pubmed: 32553273
Clin Infect Dis. 2020 Dec 3;71(9):2428-2446
pubmed: 32215622
Am J Physiol Lung Cell Mol Physiol. 2011 Mar;300(3):L341-53
pubmed: 21131395
Int J Immunopathol Pharmacol. 2016 Jun;29(2):195-204
pubmed: 26781462
Cell Host Microbe. 2020 Jul 8;28(1):124-133.e4
pubmed: 32485164
Nat Rev Neurol. 2020 Aug;16(8):403
pubmed: 32591754
Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18607-18612
pubmed: 31451661
J Neuropathol Exp Neurol. 2001 Dec;60(12):1127-36
pubmed: 11764086
Nat Commun. 2015 Oct 13;6:8533
pubmed: 26460802
J Virol. 2020 Mar 17;94(7):
pubmed: 31996437
Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1896-903
pubmed: 11734443
Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):E5636-44
pubmed: 27601645
Cell. 2020 Jul 9;182(1):50-58.e8
pubmed: 32516571
Microbiol Mol Biol Rev. 2012 Mar;76(1):16-32
pubmed: 22390970
Hong Kong Med J. 2005 Jun;11(3):189-99
pubmed: 15951584
Nature. 2020 Jul;583(7818):830-833
pubmed: 32380511
Mol Ther. 2003 May;7(5 Pt 1):649-58
pubmed: 12718908
Cell. 2020 Aug 6;182(3):734-743.e5
pubmed: 32643603
J Infect. 2020 Jun;80(6):607-613
pubmed: 32283152
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
JCI Insight. 2020 Oct 2;5(19):
pubmed: 32841215
Nat Commun. 2020 Nov 17;11(1):5838
pubmed: 33203860
Cell Host Microbe. 2020 Jun 10;27(6):883-890.e2
pubmed: 32407669
J Exp Med. 2020 Dec 7;217(12):
pubmed: 32750141
Science. 2020 Aug 14;369(6505):806-811
pubmed: 32434945
Science. 2020 Aug 14;369(6505):812-817
pubmed: 32434946
Front Immunol. 2018 Nov 09;9:2589
pubmed: 30473701
Nat Med. 2005 Aug;11(8):875-9
pubmed: 16007097
Cytokine Growth Factor Rev. 2020 Jun;53:25-32
pubmed: 32446778
Nat Med. 2004 Sep;10(9):927-34
pubmed: 15311275
Nat Immunol. 2020 Oct;21(10):1146-1151
pubmed: 32855555
Cancer Immunol Res. 2014 Apr;2(4):288-94
pubmed: 24764575
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Cell Host Microbe. 2020 Jun 10;27(6):879-882.e2
pubmed: 32359396
Cytokine Growth Factor Rev. 2020 Aug;54:62-75
pubmed: 32513566
J Virol. 2007 Jun;81(11):5429-36
pubmed: 17182688
Cell. 2020 May 14;181(4):894-904.e9
pubmed: 32275855
J Vasc Surg. 2018 Apr;67(4):1248-1262
pubmed: 28434701
Nature. 2020 Jul;583(7816):437-440
pubmed: 32434211
Nat Immunol. 2020 Nov;21(11):1327-1335
pubmed: 32839612