Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

Israelow, B. et al. (2020) Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal of Experimental Medicine, 217(12), e20201241. (doi: 10.1084/jem.20201241) (PMID:32750141) (PMCID:PMC7401025)

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Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus’s inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)–mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Meir Ben Efraim, Dr Amit
Authors: Israelow, B., Song, E., Mao, T., Lu, P., Meir, A., Liu, F., Alfajaro, M. M., Wei, J., Dong, H., Homer, R. J., Ring, A., Wilen, C. B., and Iwasaki, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN (Online):1540-9538
Published Online:04 August 2020
Copyright Holders:Copyright © 2020 Israelow et al.
First Published:First published in Journal of Experimental Medicine 217(12): e20201241
Publisher Policy:Reproduced under a Creative Commons License

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