COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.

COVID-19 自 2019 年以来已在全球范围内传播，目前对公共健康构成严重威胁。我们之前将病原体鉴定为一种新型 SARS 相关冠状病毒 (SARS-CoV-2)，它使用人血管紧张素转换酶 2 (hACE2) 作为进入受体。在这里，我们成功开发了SARS-CoV-2 hACE2转基因小鼠（C3B6小鼠中的HFH4-hACE2）感染模型。受感染的小鼠产生了典型的间质性肺炎和与 COVID-19 患者相似的病理学。病毒定量显示肺部是主要感染部位，尽管在一些小鼠的眼睛、心脏和大脑中也发现了病毒 RNA。从受感染的肺和脑组织中分离出全基因组序列与 SARS-CoV-2 相同的病毒。最后，我们证明预先暴露于 SARS-CoV-2 可以保护小鼠免受严重肺炎的侵害。我们的结果表明 hACE2 小鼠将成为测试潜在疫苗和治疗方法的宝贵工具。