Ifnar1-KO Mouse

Ifnar1, the interferon alpha receptor 1, is a crucial subunit of the type I interferon receptor (IFNAR). Type I interferon signaling, in which Ifnar1 is involved, plays a vital role in the body's innate and adaptive antiviral immunity, participating in multiple biological processes such as host defense against pathogen invasion and regulation of the immune response [1,4]. Genetic models, like gene knockout (KO) mouse models, have been essential for studying its function.

In Ifnar1 -deficient models, several significant findings have emerged. Genetic ablation of Ifnar1 specifically in natural killer (NK) cells led to improved antiviral T cell function and hastened virus clearance, indicating that Ifnar1 signaling in NK cells promotes persistent virus infection [2]. In tumor -draining lymph nodes, Ifnar1 -deficient mice showed elevated neutrophil accumulation but impaired neutrophil capacity to interact with and stimulate T -cells, contributing to enhanced tumor growth [3]. Additionally, IFNAR1 -/- mice infected with SFTS virus exhibited activation of neurotoxic A1 -reactive astrocytes, accelerating fatal brain damage [5]. An IFNAR1 knockout Madin-Darby bovine kidney (MDBK) cell line showed increased titers of bovine viruses, and RNA -seq revealed reduced expression of genes related to IFN-I pathways [6].

In conclusion, Ifnar1 is central to the body's antiviral immune response and is involved in processes related to virus control, tumor immunity, and neuroinflammation. The study of Ifnar1 using KO mouse models and other cell-based knockout models has provided valuable insights into its role in these disease-related biological processes, which may contribute to the development of new therapeutic strategies.

References:

1. López-Bielma, María Fernanda, Falfán-Valencia, Ramcés, Abarca-Rojano, Edgar, Pérez-Rubio, Gloria. 2023. Participation of Single-Nucleotide Variants in IFNAR1 and IFNAR2 in the Immune Response against SARS-CoV-2 Infection: A Systematic Review. In Pathogens (Basel, Switzerland), 12, . doi:10.3390/pathogens12111320. https://pubmed.ncbi.nlm.nih.gov/38003785/

2. Huang, Zhe, Kang, Seung Goo, Li, Yunqiao, Teijaro, John R, Xiao, Changchun. 2021. IFNAR1 signaling in NK cells promotes persistent virus infection. In Science advances, 7, . doi:10.1126/sciadv.abb8087. https://pubmed.ncbi.nlm.nih.gov/33771858/

3. Hussain, Timon, Domnich, Maksim, Bordbari, Sharareh, Lang, Stephan, Jablonska, Jadwiga. 2022. IFNAR1 Deficiency Impairs Immunostimulatory Properties of Neutrophils in Tumor-Draining Lymph Nodes. In Frontiers in immunology, 13, 878959. doi:10.3389/fimmu.2022.878959. https://pubmed.ncbi.nlm.nih.gov/35833131/

4. Kirou, Kyriakos A, Dall Era, Maria, Aranow, Cynthia, Anders, Hans-Joachim. 2022. Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. In Frontiers in immunology, 13, 980079. doi:10.3389/fimmu.2022.980079. https://pubmed.ncbi.nlm.nih.gov/36119023/

5. Kim, Seon-Hee, Choi, Ha Nyeoung, Jo, Min Gi, Hong, Kyung-Wook, Yun, Seung Pil. . Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice. In Journal of medical virology, 96, e29854. doi:10.1002/jmv.29854. https://pubmed.ncbi.nlm.nih.gov/39135475/

6. Geng, Yuanchen, Jiang, Chuanwen, Yang, Hao, Hu, Changmin, Guo, Aizhen. 2024. Construction of an IFNAR1 knockout MDBK cell line using CRISPR/Cas9 and its effect on bovine virus replication. In Frontiers in immunology, 15, 1404649. doi:10.3389/fimmu.2024.1404649. https://pubmed.ncbi.nlm.nih.gov/39100665/