Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2.

Cell
Ren-Di JiangZheng-Li Shi

Abstract

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.

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Datasets Mentioned

BETA
MT163720

Methods Mentioned

BETA
transgenic
confocal microscopy
bronchoalveolar lavage
blood collection
PCR

Key Resources (RRID) Mentioned

CVCL_0574

Software Mentioned

Geneious Geneious
GraphPad
Pannoramic Viewer
BLAST
PRISM
StepOne
Geneious
GraphPad Prism

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