TY - JOUR
AU - Israelow, Benjamin
AU - Song, Eric
AU - Mao, Tianyang
AU - Lu, Peiwen
AU - Meir, Amit
AU - Liu, Feimei
AU - Alfajaro, Mia Madel
AU - Wei, Jin
AU - Dong, Huiping
AU - Homer, Robert J.
AU - Ring, Aaron M.
AU - Wilen, Craig B.
AU - Iwasaki, Akiko
PY - 2020
DA - August
TI - Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
JO - Journal of Experimental Medicine
VL - 217
IS - 12
DO - https://doi.org/10.1084/jem.20201241
AB - 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.
PB - Rockefeller University Press
UR - https://eprints.gla.ac.uk/292088/
KW - Coronavirus (COVID-19)
ER