Severe acute respiratory syndrome CoV-2 (
SARS-CoV-2) is currently causing a worldwide
pandemic with high
morbidity and
mortality. Development of
animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of
vaccines and
antivirals, and
understanding disease pathogenesis.
SARS-CoV-2 has been shown to use the same entry receptor as
SARS-CoV-1,
human angiotensin-converting enzyme 2 (hACE2)(1-3). Due to
amino acid differences between murine and hACE2,
inbred mouse strains fail to support high titer viral replication of
SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in
mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to
adenovirus-mediated delivery of hACE2 to the
mouse lung. We show that K18-hACE2
mice replicate
virus to high titers in both the
lung and
brain leading to lethality. In contrast,
adenovirus-mediated delivery results in
viral replication to lower titers limited to the
lung, and no clinical signs of
infection with a challenge
dose of 104 plaque forming units. The K18-hACE2 model provides a stringent model for testing the
ability of
vaccines and
antivirals to protect against
disease, whereas the
adenovirus delivery system has the
flexibility to be used across multiple
genetic backgrounds and modified
mouse strains.Competing Interest StatementThe authors have declared no competing interest.View Full Text