• Emerg Microbes Infect · Dec 2020

    Comparative Study

    Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection.

    • Raveen Rathnasinghe, Shirin Strohmeier, Fatima Amanat, Virginia L Gillespie, Florian Krammer, Adolfo García-Sastre, Lynda Coughlan, Michael Schotsaert, and Melissa B Uccellini.
    • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    • Emerg Microbes Infect. 2020 Dec 1; 9 (1): 2433-2445.

    AbstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1-3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.

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