| First Author | Chauhan NR | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 11 | Pages | 113275 |
| PubMed ID | 37874678 | Mgi Jnum | J:342325 |
| Mgi Id | MGI:7548220 | Doi | 10.1016/j.celrep.2023.113275 |
| Citation | Chauhan NR, et al. (2023) Transgenic mouse models support a protective role of type I IFN response in SARS-CoV-2 infection-related lung immunopathology and neuroinvasion. Cell Rep 42(11):113275 |
| abstractText | Type I 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 infection remains 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 infection. In contrast, a severe SARS-CoV-2 infection along with immune cell 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 phenotype observed in hACE2; Irgm1(-/-) mice, suggesting that heightened IFN-I response accounts for the observed immunity. Taking the results 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. |
