tetano
Editor, Senior Moderator
J Exp Med
. 2020 Dec 7;217(12):e20201241.
doi: 10.1084/jem.20201241.
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Benjamin Israelow[SUP] 1 2 [/SUP], Eric Song[SUP] 1 [/SUP], Tianyang Mao[SUP] 1 [/SUP], Peiwen Lu[SUP] 1 [/SUP], Amit Meir[SUP] 3 [/SUP], Feimei Liu[SUP] 1 [/SUP], Mia Madel Alfajaro[SUP] 1 4 [/SUP], Jin Wei[SUP] 1 4 [/SUP], Huiping Dong[SUP] 1 [/SUP], Robert J Homer[SUP] 5 [/SUP], Aaron Ring[SUP] 1 [/SUP], Craig B Wilen[SUP] 1 4 [/SUP], Akiko Iwasaki[SUP] 1 6 [/SUP]
Affiliations
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.
. 2020 Dec 7;217(12):e20201241.
doi: 10.1084/jem.20201241.
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Benjamin Israelow[SUP] 1 2 [/SUP], Eric Song[SUP] 1 [/SUP], Tianyang Mao[SUP] 1 [/SUP], Peiwen Lu[SUP] 1 [/SUP], Amit Meir[SUP] 3 [/SUP], Feimei Liu[SUP] 1 [/SUP], Mia Madel Alfajaro[SUP] 1 4 [/SUP], Jin Wei[SUP] 1 4 [/SUP], Huiping Dong[SUP] 1 [/SUP], Robert J Homer[SUP] 5 [/SUP], Aaron Ring[SUP] 1 [/SUP], Craig B Wilen[SUP] 1 4 [/SUP], Akiko Iwasaki[SUP] 1 6 [/SUP]
Affiliations
- PMID: 32750141
- DOI: 10.1084/jem.20201241
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.