Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
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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.
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SciScore for 10.1101/2020.05.27.118893: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources To assess the capacity for B6J AAV-hACE2 mice to mount an antibody response to SARS-CoV-2 challenge , we quantified anti spike protein IgG titers by ELISA9,10 . anti spike protein IgGsuggested: NoneWe found that while control infected mice did not develop anti-spike antibodies , AAV-hACE2 B6/J mice mounted a significant antibody response between 4- and 7- DPI , which continued to increase at 14 DPI ( Fig . 1h) . SciScore for 10.1101/2020.05.27.118893: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources To assess the capacity for B6J AAV-hACE2 mice to mount an antibody response to SARS-CoV-2 challenge , we quantified anti spike protein IgG titers by ELISA9,10 . anti spike protein IgGsuggested: NoneWe found that while control infected mice did not develop anti-spike antibodies , AAV-hACE2 B6/J mice mounted a significant antibody response between 4- and 7- DPI , which continued to increase at 14 DPI ( Fig . 1h) . anti-spikesuggested: NoneNext , to assess the neutralization potential of these antibodies , we performed plaque reduction neutralization assay ( PRNT ) using SARS-CoV-2 , and found PRNT75 at a serum dilution of 1:1024 as early as 7 DPI ( Fig 1i) SARS-CoV-2suggested: (Sino Biological Cat# 40143-R019, AB_2827973)Software and Algorithms Sentences Resources Using the Interferome database ( http://www.interferome.org/) , we mapped the top upregulated genes to their transcriptional regulation by either type I , II , or III IFNs ( Fig . 2b) . http://www.interferome.org/suggested: (Interferome, SCR_007743)Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
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