A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection.
Antiviral Res
; 193: 105138, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1300619
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Disease Models, Animal
/
SARS-CoV-2
/
COVID-19
/
Lung
Type of study:
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Antiviral Res
Year:
2021
Document Type:
Article
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