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.
【저자키워드】 SARS-CoV-2, viral infection, 【초록키워드】 Vaccine, Cytokine storm, Pathogenesis, Antiviral, Therapeutics, SARS-COV-2 infection, viral pathogenesis, Infection, lung, animal model, cytokine, animal models, Prophylactic, virus, angiotensin converting enzyme, chemokine, Brain, hACE2, COVID-19 disease, Viral, mice, therapeutic, severe COVID-19 disease, spleen, K18-hACE2, Human angiotensin-converting enzyme 2, angiotensin, airway epithelium, lethality, both lungs, characterization, enzyme, human Angiotensin-converting enzyme, human angiotensin converting enzyme 2, transgenic mice, cytokeratin 18 promoter, susceptible, benefit, produced, peaked, induce, expressing, K18, 【제목키워드】 K18,