Transgenic Mouse Models Support a Protective Role of Type 1 IFN Response in SARS-CoV-2 infection-related Lung Immunopathology and Neuroinvasion

Published: 18 September 2023| Version 1 | DOI: 10.17632/59nr9kd5xy.1
Santosh Chauhan


Western blot data of figures. Abstrct Type 1 interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infections remained to be perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1-/-) and the other with dampened IFN-I response (hACE2; Ifnar1-/-) to comprehend the role of IFN-I response. We report that hACE2; Irgm1-/- mice are resistant to lethal SARS-CoV-2 infections. In contrast, a severe SARS-CoV-2 infection along with immune cells infiltration, cytokine storm, and enhanced pathology is observed in the lungs and brain of hACE2; Ifnar1-/- mice. The hACE2; Irgm1-/-Ifnar1-/- double knockout mice display loss of the protective phenotypes observed in hACE2; Irgm1-/- mice suggesting that heightened IFN-I response accounts for the observed immunity. Together, we demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against SARS-CoV-2.



Institute of Life Sciences, Centre for Cellular and Molecular Biology CSIR


Antiviral Immune Response