1. Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice
- Author
-
Andreu Garcia-Vilanova, Corbett Christie, Edward J. Dick, Jordi B. Torrelles, Hilary M. Staples, Kendra J. Alfson, Luis D. Giavedoni, Jun-Gyu Park, Tim J. Anderson, Kevin Chiem, Olga Gonzalez, Juan Ignacio García, Larry S. Schlesinger, Laura M. Parodi, Jean L. Patterson, Varun Dwivedi, Deepak Kaushal, Shannan Hall-Ursone, Colin Chuba, Ricardo Carrion, Chengjin Ye, Katrina N. Kavelish, Angélica Olmo-Fontánez, Stephanie Earley, Luis Martinez-Sobrido, Xavier Alvarez, Cory R. A. Hallam, Stephanie Davis Mdaki, Anna Allué-Guardia, Roy N. Platt, Renee Escalona, Paula A. Pino, Alyssa Schami, Colwyn A. Headley, Michal Gazi, Jesse Martinez, Shalini Gautam, Oscar H. Rodriguez, Fatai S. Oladunni, Joanne Turner, Alison Whigham, and Anwari Akhter
- Subjects
0301 basic medicine ,Genetically modified mouse ,Chemokine ,Science ,Viral pathogenesis ,Transgene ,General Physics and Astronomy ,Mice, Transgenic ,Respiratory Mucosa ,macromolecular substances ,Article ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Pathogenesis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Genetic Predisposition to Disease ,Mortality ,Promoter Regions, Genetic ,Lung ,Multidisciplinary ,Keratin-18 ,biology ,SARS-CoV-2 ,Brain ,COVID-19 ,General Chemistry ,respiratory system ,medicine.disease ,Virology ,respiratory tract diseases ,Disease Models, Animal ,030104 developmental biology ,Virus Diseases ,Viral infection ,Angiotensin-converting enzyme 2 ,biology.protein ,Angiotensin-Converting Enzyme 2 ,Disease Susceptibility ,Cytokine Release Syndrome ,Cytokine storm ,030217 neurology & neurosurgery - 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., Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.
- Published
- 2020
- Full Text
- View/download PDF