Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Rathnasinghe, Raveen; Strohmeier, Shirin; Amanat, Fatima; Gillespie, Virginia L.; Krammer, Florian; García-Sastre, Adolfo; Coughlan, Lynda; Schotsaert, Michael; Uccellini, Melissa B.
• Is Part Of: Emerging microbes & infections. Volume 9:Issue 1(2020)
• Page Start: 2433
• Page End: 2445
• Publication Date: 2020-01-01
• Subjects: SARS-CoV-2 -- COVID-19 -- ACE2 -- adenovirus -- mouse models; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2020.1838955
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: Severe 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.