Israelow et al. report a novel mouse model of COVID-19 using adeno-associated virus (AAV)-mediated expression of human ACE2 (hACE2) in the respiratory tract, which supports productive SARS-CoV-2 infection. Infected mice had acute infiltration of innate and adaptive immune cells to the lungs and developed specific neutralizing antibodies. Transcriptomic analysis showed robust upregulation of cytokines and of interferon-stimulated genes (ISGs), largely overlapping with the signature seen in patient lungs. A key advantage of this model is its application to mice of different genetic backgrounds and age. Infection of AAV–hACE2 mice lacking IFNAR1 or IRF3 and IRF7 showed that type I interferon signalling is required for ISG expression and the recruitment of pro-inflammatory cells to the lungs during infection. Potential future applications of this model include testing therapeutics and vaccines for COVID-19.
Israelow, B. et al. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Preprint at bioRxiv https://doi.org/10.1101/2020.05.27.118893 (2020)
The authors declare no competing interests.
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Borrmann, H., Rigby, R.E. A versatile mouse model of COVID-19. Nat Rev Immunol 20, 460 (2020). https://doi.org/10.1038/s41577-020-0369-3