Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice

Nature Communications
Fatai S OladunniJordi B Torrelles

Abstract

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.

References

Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·W Y ParkT R Martin
Jan 5, 2002·Journal of Neuropathology and Experimental Neurology·K BiernackiJ P Antel
Apr 30, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gabriele ToiettaArthur L Beaudet
Aug 18, 2004·Nature Medicine·Juan E Moyron-QuirozTroy D Randall
Dec 17, 2004·Journal of Medical Virology·Kao-Jean HuangHuan-Yao Lei
Dec 22, 2006·Journal of Virology·Eric LofgrenE N Naumova
Dec 7, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Lei SunThomas P Shanley
Mar 7, 2012·Microbiology and Molecular Biology Reviews : MMBR·Jennifer R TisoncikMichael G Katze
Oct 23, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sachin P GadaniJonathan Kipnis
Apr 26, 2014·Cancer Immunology Research·Toshio Tanaka, Tadamitsu Kishimoto
Jun 4, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria Teresa P de AquinoStephen A Stohlman
Apr 12, 2015·Annual Review of Immunology·Hiroki Yoshida, Christopher A Hunter
Jan 20, 2016·International Journal of Immunopathology and Pharmacology·Adam AntczakEwa Brzeziańska-Lasota
Feb 16, 2016·Trends in Immunology·Aleksandra DeczkowskaMichal Schwartz
Sep 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·Taylor W ForemanDeepak Kaushal
Apr 25, 2017·Journal of Vascular Surgery·Satomi KasashimaKengo Kawakami
Nov 27, 2018·Frontiers in Immunology·Kelly M ShepardsonAgnieszka Rynda-Apple
Aug 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Adam D KenneyJacob S Yount
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 28, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jasper Fuk-Woo ChanKwok-Yung Yuen
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 14, 2020·The Journal of Infection·Qing YeJianhua Mao
Apr 18, 2020·Critical Care : the Official Journal of the Critical Care Forum·Luciano GattinoniSandra Rossi
May 4, 2020·Cell Host & Microbe·Eugenia Ziying OngJenny Guek Hong Low
May 8, 2020·Nature·Linlin BaoChuan Qin
May 15, 2020·Cell Host & Microbe·Zhuo ZhouJianwei Wang
May 21, 2020·Nature·Xiaonan ZhangHongzhou Lu
May 22, 2020·Science·Jingyou YuDan H Barouch
May 22, 2020·Science·Abishek ChandrashekarDan H Barouch
May 25, 2020·Cytokine & Growth Factor Reviews·Francesca CoperchiniMario Rotondi
Jun 3, 2020·Cell Host & Microbe·Shi-Hui SunYou-Chun Wang
Jun 9, 2020·BioRxiv : the Preprint Server for Biology·Courtney WoolseyRobert W Cross
Jun 10, 2020·Cytokine & Growth Factor Reviews·Víctor J Costela-RuizLucia Melguizo-Rodríguez
Jun 13, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Peipei SongChongge You

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Citations

Jan 30, 2021·Journal of Virological Methods·Fatai S OladunniLuis Martinez-Sobrido
Feb 12, 2021·Frontiers in Immunology·Ramachandran VigneshPachamuthu Balakrishnan
Feb 13, 2021·Life Science Alliance·Prabhuanand SelvarajTony T Wang
Apr 5, 2021·EBioMedicine·Martin S WinklerMarcin F Osuchowski
Apr 8, 2021·Nature Reviews. Microbiology·Tim FlerlageStacey Schultz-Cherry
Apr 10, 2021·ILAR Journal·Caroline J ZeissRebecca Terilli Veenhuis
Apr 30, 2021·ILAR Journal·Rebecca T Veenhuis, Caroline J Zeiss
May 7, 2021·Scientific Reports·C Joaquín CáceresDaniel R Perez
May 9, 2021·Nature Immunology·Min ZhengThirumala-Devi Kanneganti
May 23, 2021·Cell Host & Microbe·Shea A LoweryStanley Perlman
Jun 3, 2021·Medical Sciences : Open Access Journal·Christina BorchersRavi P Sahu
Jun 23, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ruben Colunga BiancatelliJohn D Catravas

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Datasets Mentioned

BETA
MN985325.1
MT576563

Methods Mentioned

BETA
transgenic
bronchoalveolar lavage
sedation
ELISA
enzyme-linked immunosorbent assays
light microscopy
confocal microscopy

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