ABSTRACT 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 the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, Adenovirus, Mouse models, 【초록키워드】 coronavirus disease, Vaccine, antivirals, Infection, lung, SARS-CoV-2 virus, animal model, virus, SARS-CoV-1, Brain, hACE2, Replication, viral replication, K18-hACE2 mice, morbidity and mortality, development, Strains, Critical, K18-hACE2, Amino acid, strain, nasal turbinate, nasal turbinates, Support, disease pathogenesis, acute respiratory syndrome, worldwide pandemic, human Angiotensin-converting enzyme, entry receptor, genetic background, Clinical sign, murine, transgenic, shown, replicate, provide, in viral, transgenic model, 【제목키워드】 SARS-COV-2 infection, hACE2, mouse model, transgenic,