First Author | Israelow B | Year | 2020 |
Journal | J Exp Med | Volume | 217 |
Issue | 12 | PubMed ID | 32750141 |
Mgi Jnum | J:291862 | Mgi Id | MGI:6448510 |
Doi | 10.1084/jem.20201241 | Citation | Israelow B, et al. (2020) Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. J Exp Med 217(12) |
abstractText | 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. |