Journal of Virology
Volume 96 Number 1 January 2022
http://jvi.asm.org/content/current

SARS-CoV-2 Infection in Human ACE2 Knock-In Mice
Mouse models of SARS-CoV-2 pathogenesis have facilitated the rapid evaluation of antibody and vaccine countermeasures. While the first generation of models developed severe disease after SARS-CoV-2 infection, they relied on ectopic expression of supraphysiological levels of human ACE2 (hACE2). Winkler et al. (e01511-21) evaluated SARS-CoV-2 infection in hACE2 knock-in (KI) mice, which express hACE2 under an endogenous promoter in place of murine ACE2. Infection of hACE2 KI mice with historical or variant SARS-CoV-2 strains resulted in replication within the respiratory tract but did not cause severe pulmonary injury. Thus, the hACE2 KI mouse can serve as a model of mild SARS-CoV-2 lung infection