Abstract
Although animal models have been evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, none have fully recapitulated the lung disease phenotypes seen in humans who have been hospitalized. Here, we evaluate transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs, with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of nuclear factor-κB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.
【초록키워드】 Monocytes, SARS-CoV-2, viral infection, ACE2, coronavirus, Hospitalized, innate immune response, SARS-COV-2 infection, Human, neutrophil, Infection, Lung disease, animal model, immune, Pulmonary function, Lungs, phenotype, K18-hACE2 mice, interferon signaling, receptor, K18-hACE2, infiltration, Pathways, Severe COVID-19 Infection, acute respiratory syndrome, leukocyte activation, enzyme, type I, other organs, transgenic mice, lung tissue, activated T cells, promoter, nuclear, viral titer, feature, evaluate, spread to, evaluated, can be used, occur, to define, upregulated, expressing, driven by, K18, 【제목키워드】 SARS-COV-2 infection, mice, severe lung inflammation, impaired function, cause,