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

Oladunni, Fatai S.; Park, Jun-Gyu; Pino, Paula A.; Gonzalez, Olga; Akhter, Anwari; Allué-Guardia, Anna; Olmo-Fontánez, Angélica; Gautam, Shalini; Garcia-Vilanova, Andreu; Ye, Chengjin; Chiem, Kevin; Headley, Colwyn; Dwivedi, Varun; Parodi, Laura M.; Alfson, Kendra J.; Staples, Hilary M.; Schami, Alyssa; Garcia, Juan I.; Whigham, Alison; Platt, Roy Neal; Gazi, Michal; Martinez, Jesse; Chuba, Colin; Earley, Stephanie; Rodriguez, Oscar H.; Mdaki, Stephanie Davis; Kavelish, Katrina N.; Escalona, Renee; Hallam, Cory R. A.; Christie, Corbett; Patterson, Jean L.; Anderson, Tim J. C.; Carrion, Ricardo; Dick, Edward J.; Hall-Ursone, Shannan; Schlesinger, Larry S.; Alvarez, Xavier; Kaushal, Deepak; Giavedoni, Luis D.; Turner, Joanne; Martinez-Sobrido, Luis; Torrelles, Jordi B.

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

Fatai S. Oladunni, Jun-Gyu Park, Paula A. Pino, Olga Gonzalez, Anwari Akhter, Anna Allué-Guardia, Angélica Olmo-Fontánez, Shalini Gautam, Andreu Garcia-Vilanova, Chengjin Ye, Kevin Chiem, Colwyn Headley, Varun Dwivedi, Laura M. Parodi, Kendra J. Alfson, Hilary M. Staples, Alyssa Schami, Juan I. Garcia, Alison Whigham, Roy Neal Platt, Michal Gazi, Jesse Martinez, Colin Chuba, Stephanie Earley, Oscar H. Rodriguez, Stephanie Davis Mdaki, Katrina N. Kavelish, Renee Escalona, Cory R. A. Hallam, Corbett Christie, Jean L. Patterson, Tim J. C. Anderson, Ricardo Carrion, Edward J. Dick, Shannan Hall-Ursone, Larry S. Schlesinger, Xavier Alvarez, Deepak Kaushal, Luis D. Giavedoni, Joanne Turner (), Luis Martinez-Sobrido () and Jordi B. Torrelles ()
Additional contact information
Fatai S. Oladunni: Texas Biomedical Research Institute
Jun-Gyu Park: Texas Biomedical Research Institute
Paula A. Pino: Texas Biomedical Research Institute
Olga Gonzalez: Texas Biomedical Research Institute
Anwari Akhter: Texas Biomedical Research Institute
Anna Allué-Guardia: Texas Biomedical Research Institute
Angélica Olmo-Fontánez: Texas Biomedical Research Institute
Shalini Gautam: Texas Biomedical Research Institute
Andreu Garcia-Vilanova: Texas Biomedical Research Institute
Chengjin Ye: Texas Biomedical Research Institute
Kevin Chiem: Texas Biomedical Research Institute
Colwyn Headley: Texas Biomedical Research Institute
Varun Dwivedi: Texas Biomedical Research Institute
Laura M. Parodi: Texas Biomedical Research Institute
Kendra J. Alfson: Texas Biomedical Research Institute
Hilary M. Staples: Texas Biomedical Research Institute
Alyssa Schami: Texas Biomedical Research Institute
Juan I. Garcia: Texas Biomedical Research Institute
Alison Whigham: Texas Biomedical Research Institute
Roy Neal Platt: Texas Biomedical Research Institute
Michal Gazi: Texas Biomedical Research Institute
Jesse Martinez: Texas Biomedical Research Institute
Colin Chuba: Texas Biomedical Research Institute
Stephanie Earley: Texas Biomedical Research Institute
Oscar H. Rodriguez: Texas Biomedical Research Institute
Stephanie Davis Mdaki: Texas Biomedical Research Institute
Katrina N. Kavelish: Texas Biomedical Research Institute
Renee Escalona: Texas Biomedical Research Institute
Cory R. A. Hallam: Texas Biomedical Research Institute
Corbett Christie: Texas Biomedical Research Institute
Jean L. Patterson: Texas Biomedical Research Institute
Tim J. C. Anderson: Texas Biomedical Research Institute
Ricardo Carrion: Texas Biomedical Research Institute
Edward J. Dick: Texas Biomedical Research Institute
Shannan Hall-Ursone: Texas Biomedical Research Institute
Larry S. Schlesinger: Texas Biomedical Research Institute
Xavier Alvarez: Texas Biomedical Research Institute
Deepak Kaushal: Texas Biomedical Research Institute
Luis D. Giavedoni: Texas Biomedical Research Institute
Joanne Turner: Texas Biomedical Research Institute
Luis Martinez-Sobrido: Texas Biomedical Research Institute
Jordi B. Torrelles: Texas Biomedical Research Institute

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19891-7

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