@article{Israelow_B-2020_112187,
title = {Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling},
author = {Israelow, B. and Song, E. and Mao, T. and Lu, P. and Meir, A. and Liu, F. and Alfajaro, M. and Wei, J. and Dong, H. and Homer, R. and Ring, A. and Wilen, C. and Iwasaki, A.},
month = {aug},
year = {2020},
abstract = {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.},
volume = {217},
issue = {12},
journal = {Journal of Experimental Medicine},
publisher = {Rockefeller University Press},
url = {https://doi.org/10.1084/jem.20201241},
}
