• Ahmed O Hassan, James Brett Case, Emma S Winkler, Larissa B Thackray, Natasha M Kafai, Adam L Bailey, Broc T McCune, Julie M Fox, Rita E Chen, Wafaa B Alsoussi, Jackson S Turner, Aaron J Schmitz, Tingting Lei, Swathi Shrihari, Shamus P Keeler, Daved H Fremont, Suellen Greco, Paul B McCray, Stanley Perlman, Michael J Holtzman, Ali H Ellebedy, and Michael S Diamond.
• Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
• Cell. 2020 Aug 6; 182 (3): 744-753.e4.

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.Copyright © 2020 Elsevier Inc. All rights reserved.

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