LAUSR

Significance Human coronavirus 229E(HCoV-229E) and NL63 (HCoV-NL63) are endemic worldwide and cause mild upper respiratory infections or occasionally, more severe lower respiratory tract infections. Mice are not permissive to these virus infections primarily because they lack receptors for these viruses. The recent emergence of COVID-19 emphasizes the need to develop animal models for these CoVs. Here, we generated mouse models for 229E and NL63 by exogenous delivery of their receptors, hAPN and hACE2, respectively, using adenoviruses. We show that these mouse models are useful for analyzing immune responses and for evaluating vaccines and potential therapeutic drugs against HCoV-229E and HCoV-NL63. Moreover, CCCoV-infected mice were partially protected from SARS-CoV-2 infection.