Modeling epithelial and endothelial cell tropism for SARS-CoV-2 through restricted transgenic hACE2 expression in mice
Lameire, S.; Debeuf, N.; Deckers, J.; De Wolf, C.; Vanheerswynghels, M.; Toussaint, W.; De Vlieger, L.; Van Hoecke, L.; De Cae, S.; Schepens, B.; Vanhee, S.; Lambrecht, B. N.
Show abstract
Severe COVID-19 is frequently associated with vascular complications, raising ongoing debate about whether SARS-CoV-2 can directly infect endothelial cells and thereby contribute to disease pathogenesis. Although endothelial cells express angiotensin-converting enzyme 2 (ACE2), the in vivo relevance of endothelial-restricted viral tropism remains unclear. To directly assess the consequences of endothelial-restricted SARS-CoV-2 tropism in vivo, we generated a transgenic mouse model expressing human ACE2 under control of the endothelial-specific Cdh5 promoter (Cdh5-hACE2). Despite confirmed pulmonary endothelial expression and protein presence of hACE2, SARS-CoV-2 infection of Cdh5-hACE2 mice did not induce clinical illness, detectable viral replication, immune cell influx in the lung, or histopathological abnormalities in the lung or brain. These findings indicate that endothelial-restricted SARS-CoV-2 tropism alone is insufficient to drive productive infection and clinical disease in vivo, suggesting that endothelial involvement in COVID-19 likely arises in the context of broader cellular infection or systemic host responses rather than from primary endothelial infection.
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