Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
- PMID: 32750141
- PMCID: PMC7401025
- DOI: 10.1084/jem.20201241
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
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 Israelow et al.
Conflict of interest statement
Disclosures: A. Ring reported a patent to novel binding partner that interacts with SARS-CoV2 spike N-terminal domain pending; reports, "Unrelated to the subject of the work, I have founded, co-founded, and/or hold equity in biotechnology companies including Simcha Therapeutics, Forty Seven Inc., and ALX Oncology. I have also consulted for Medicenna Therapeutics, a company that licensed patents I invented in immuno-oncology. None of these companies are in the SARS-CoV-2 space or work on infectious disease to my knowledge. Broadly related to the subject of this work, within the past year, I have purchased and disposed shares in Gilead Sciences and Vir Biotechnology, which are working on therapeutics in the coronavirus space. I currently hold no shares in either of those companies." No other disclosures were reported.
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Update of
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Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling.bioRxiv [Preprint]. 2020 May 27:2020.05.27.118893. doi: 10.1101/2020.05.27.118893. bioRxiv. 2020. Update in: J Exp Med. 2020 Dec 7;217(12):e20201241. doi: 10.1084/jem.20201241. PMID: 32577647 Free PMC article. Updated. Preprint.
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Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling.SSRN [Preprint]. 2020 Jun 16:3628297. doi: 10.2139/ssrn.3628297. SSRN. 2020. Update in: J Exp Med. 2020 Dec 7;217(12):e20201241. doi: 10.1084/jem.20201241. PMID: 32714125 Free PMC article. Updated. Preprint.
Comment in
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An ace model for SARS-CoV-2 infection.J Exp Med. 2020 Dec 7;217(12):e20201748. doi: 10.1084/jem.20201748. J Exp Med. 2020. PMID: 33000129 Free PMC article.
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