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

Autor:	Rathnasinghe R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, NY, USA.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Amanat F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Gillespie VL; The Center for Comparative Medicine and Surgery (CCMS) Comparative Pathology Laboratory, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, NY, USA.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, USA., Coughlan L; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Microbiology and Immunology and Center for Vaccine Development and Global Health (CVD), University of Maryland School of Medicine, Baltimore, USA., Schotsaert M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, NY, USA., Uccellini MB; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, NY, USA.
Jazyk:	angličtina
Zdroj:	Emerging microbes & infections [Emerg Microbes Infect] 2020 Dec; Vol. 9 (1), pp. 2433-2445.
DOI:	10.1080/22221751.2020.1838955
Abstrakt:	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.
Databáze:	MEDLINE
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