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Title: A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection
Authors: Gan, Esther S. 
Syenina, Ayesa 
Linster, Martin 
Ng, Benson
Zhang, Summer L. 
Watanabe, Satoru 
Rajarethinam, Ravisankar
Tan Hwee Cheng 
Smith, Gavin J. D. 
Ooi, Eng Eong 
Keywords: Genetic variants
K18-hACE2 mice
Issue Date: 1-Sep-2021
Publisher: Elsevier B.V.
Citation: Gan, Esther S., Syenina, Ayesa, Linster, Martin, Ng, Benson, Zhang, Summer L., Watanabe, Satoru, Rajarethinam, Ravisankar, Tan Hwee Cheng, Smith, Gavin J. D., Ooi, Eng Eong (2021-09-01). A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection. Antiviral Research 193 : 105138. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The global spread of SARS-CoV-2 has made millions ill with COVID-19 and even more from the economic fallout of this pandemic. Our quest to test new therapeutics and vaccines require small animal models that replicate disease phenotypes seen in COVID-19 cases. Rodent models of SARS-CoV-2 infection thus far have shown mild to moderate pulmonary disease; mortality, if any, has been associated with prominent signs of central nervous system (CNS) infection and dysfunction. Here we describe the isolation of SARS-CoV-2 variants with propensity for either pulmonary or CNS infection. Using a wild-type SARS-CoV-2 isolated from a COVID-19 patient, we first found that infection was lethal in transgenic mice expressing the human angiotensin I-converting enzyme 2 (hACE2). Fortuitously, full genome sequencing of SARS-CoV-2 from the brain and lung of these animals showed genetic differences. Likewise, SARS-CoV-2 isolates from brains and lungs of these also showed differences in plaque morphology. Inoculation of these brain and lung SARS-CoV-2 isolates into new batch of hACE2 mice intra-nasally resulted in lethal CNS and pulmonary infection, respectively. Collectively, our study suggests that genetic variants of SARS-CoV-2 could be used to replicate specific features of COVID-19 for the testing of potential vaccines or therapeutics. © 2021 The Authors
Source Title: Antiviral Research
ISSN: 0166-3542
DOI: 10.1016/j.antiviral.2021.105138
Rights: Attribution 4.0 International
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