Ifi27l2a, also known as interferon alpha-inducible protein 27 like 2A, is an interferon-stimulated gene. It is induced by interferons for viral host defense and has been linked to pro-inflammatory cellular mechanisms. It may play a role in multiple biological processes and diseases, and genetic models such as gene knockout mice are valuable for studying its functions [1,2,3,4].

In the context of aging and stroke, single-cell RNA sequencing showed Ifi27l2a was significantly up-regulated in microglia of aged mouse brains post-stroke. Overexpression in cultured microglia causes neuroinflammation via reactive oxygen species. Hemizygous deletion of Ifi27l2a (Ifi27l2a+/- mice) reduced gliosis, acute and chronic brain injury, and motor function deficits in an ischemic stroke model, indicating it is a critical neuroinflammatory mediator in ischemic stroke [1,2]. In viral infection studies, Ifi27l2a -/- mice were more vulnerable to lethal West Nile virus (WNV) infection, with greater viral burden in the CNS, suggesting it has an antiviral phenotype in subsets of cells [3]. However, deletion of Ifi27l2a in mice did not increase susceptibility to influenza A infection [4].

In summary, Ifi27l2a is an interferon-stimulated gene with functions in antiviral defense and neuroinflammation regulation. Mouse models, especially knockout models, have revealed its role in ischemic stroke as a key mediator of neuroinflammation, and in viral infections, showing its cell-type and region-specific antiviral activity. These findings provide potential therapeutic targets for stroke and insights into host-virus interactions [1,2,3].

References:

1. Kim, Gab Seok, Harmon, Elisabeth, Gutierrez, Manuel C, Wythe, Joshua D, Marrelli, Sean P. 2025. Single-cell analysis identifies Ifi27l2a as a gene regulator of microglial inflammation in the context of aging and stroke in mice. In Nature communications, 16, 1639. doi:10.1038/s41467-025-56847-1. https://pubmed.ncbi.nlm.nih.gov/39953063/

2. Kim, Gab Seok, Harmon, Elisabeth, Gutierrez, Manuel, Wythe, Joshua, Marrelli, Sean. 2023. Single-cell analysis identifies Ifi27l2a as a novel gene regulator of microglial inflammation in the context of aging and stroke. In Research square, , . doi:10.21203/rs.3.rs-2557290/v1. https://pubmed.ncbi.nlm.nih.gov/36824976/

3. Lucas, Tiffany M, Richner, Justin M, Diamond, Michael S. 2015. The Interferon-Stimulated Gene Ifi27l2a Restricts West Nile Virus Infection and Pathogenesis in a Cell-Type- and Region-Specific Manner. In Journal of virology, 90, 2600-15. doi:10.1128/JVI.02463-15. https://pubmed.ncbi.nlm.nih.gov/26699642/

4. Tantawy, Mohamed A, Hatesuer, Bastian, Wilk, Esther, Weiß, Siegfried, Schughart, Klaus. 2014. The interferon-induced gene Ifi27l2a is active in lung macrophages and lymphocytes after influenza A infection but deletion of Ifi27l2a in mice does not increase susceptibility to infection. In PloS one, 9, e106392. doi:10.1371/journal.pone.0106392. https://pubmed.ncbi.nlm.nih.gov/25184786/

5. Yang, Yue, Akada, Hajime, Nath, Dipmoy, Hutchison, Robert E, Mohi, Golam. 2016. Loss of Ezh2 cooperates with Jak2V617F in the development of myelofibrosis in a mouse model of myeloproliferative neoplasm. In Blood, 127, 3410-23. doi:10.1182/blood-2015-11-679431. https://pubmed.ncbi.nlm.nih.gov/27081096/

6. Jin, Yu, Wei, Changling, Huang, Xiaohan, Zhang, Li, Li, Xue. 2023. Bioinformatics Analysis and Experimental Verification of Exercise for Aging Mice in Different Brain Regions Based on Transcriptome Sequencing. In Life (Basel, Switzerland), 13, . doi:10.3390/life13101988. https://pubmed.ncbi.nlm.nih.gov/37895370/

7. Dutta, Avik, Hutchison, Robert E, Mohi, Golam. 2017. Hmga2 promotes the development of myelofibrosis in Jak2V617F knockin mice by enhancing TGF-β1 and Cxcl12 pathways. In Blood, 130, 920-932. doi:10.1182/blood-2016-12-757344. https://pubmed.ncbi.nlm.nih.gov/28637665/

8. Al-Shujairi, Wisam H, Clarke, Jennifer N, Davies, Lorena T, Pitson, Stuart M, Carr, Jillian M. 2017. Intracranial Injection of Dengue Virus Induces Interferon Stimulated Genes and CD8+ T Cell Infiltration by Sphingosine Kinase 1 Independent Pathways. In PloS one, 12, e0169814. doi:10.1371/journal.pone.0169814. https://pubmed.ncbi.nlm.nih.gov/28095439/

9. Lagor, William R, Fields, David W, Bauer, Robert C, Wherry, E John, Rader, Daniel J. 2014. Genetic manipulation of the ApoF/Stat2 locus supports an important role for type I interferon signaling in atherosclerosis. In Atherosclerosis, 233, 234-41. doi:10.1016/j.atherosclerosis.2013.12.043. https://pubmed.ncbi.nlm.nih.gov/24529150/