IFI27, also known as IFN-α-inducible protein 27, is an interferon-stimulated gene (ISG) that plays diverse roles in the immune response, metabolism, and disease [2,3,4,6,8]. It is involved in pathways such as the innate immune response, regulation of the viral life cycle, and JAK-STAT signaling pathway [2]. IFI27 has been associated with various diseases including viral infections, cancer, and inflammatory disorders, highlighting its potential as a biomarker and therapeutic target [2,3,4,5,8,9].

In adipocytes, Ifi27-knockout leads to reduced expression of key enzymes in the tricarboxylic acid cycle, subunits of the electron transport chain, and uncoupling protein 1 (Ucp1), resulting in impaired oxygen consumption and defective thermogenesis [1,7]. This indicates that Ifi27 is crucial for mitochondrial function and adipocyte thermogenic adaptation [1,7]. In the context of viral infections, overexpression of IFI27 positively regulates DENV-2 infection, while knockdown has the opposite effect [2]. In HIV-1 infection, IFI27 is upregulated and can suppress HIV-1 replication by degrading the viral gag protein through the ubiquitin-proteasome pathway [4].

In conclusion, IFI27 is a multifunctional gene. Through gene knockout studies in adipocytes, its importance in mitochondrial function and thermogenesis has been revealed. In viral infections, its role in modulating the infection process has been demonstrated, suggesting that it could be a potential therapeutic target for treating viral diseases like HIV and dengue [1,2,4,7].

References:

1. Cui, Xuan, Liu, Haojie, Shi, Ting, Tang, Qi-Qun, Pan, Dongning. 2023. IFI27 Integrates Succinate and Fatty Acid Oxidation to Promote Adipocyte Thermogenic Adaption. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2301855. doi:10.1002/advs.202301855. https://pubmed.ncbi.nlm.nih.gov/37544897/

2. Jiang, Cheng, He, Cong, Kan, Jing, Zhou, Tao, Yang, Yi. . Integrative bulk and single-cell transcriptome profiling analysis reveals IFI27 as a novel interferon-stimulated gene in dengue. In Journal of medical virology, 95, e28706. doi:10.1002/jmv.28706. https://pubmed.ncbi.nlm.nih.gov/36971141/

3. Huang, Huijuan, Lv, Jiannan, Huang, Yonglun, Li, Hongmian, Qin, Yaqin. . IFI27 is a potential therapeutic target for HIV infection. In Annals of medicine, 54, 314-325. doi:10.1080/07853890.2021.1995624. https://pubmed.ncbi.nlm.nih.gov/35068272/

4. He, Wen-Qiang, Pang, Wei, Li, Na, Yang, Liu-Meng, Zheng, Yong-Tang. 2024. IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway. In Journal of virology, 98, e0135624. doi:10.1128/jvi.01356-24. https://pubmed.ncbi.nlm.nih.gov/39475279/

5. Shojaei, Maryam, Shamshirian, Amir, Monkman, James, Short, Kirsty R, Tang, Benjamin. 2023. IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study. In Frontiers in immunology, 13, 1060438. doi:10.3389/fimmu.2022.1060438. https://pubmed.ncbi.nlm.nih.gov/36685600/

6. Villamayor, Laura, López-García, Darío, Rivero, Vanessa, Nogales, Aitor, DeDiego, Marta L. 2023. The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling. In Frontiers in microbiology, 14, 1176177. doi:10.3389/fmicb.2023.1176177. https://pubmed.ncbi.nlm.nih.gov/37187533/

7. Jin, Weiwei, Jin, Wenfang, Pan, Dongning. 2018. Ifi27 is indispensable for mitochondrial function and browning in adipocytes. In Biochemical and biophysical research communications, 501, 273-279. doi:10.1016/j.bbrc.2018.04.234. https://pubmed.ncbi.nlm.nih.gov/29730295/

8. Shojaei, Maryam, McLean, Anthony S. 2025. Interferon-stimulated gene IFI27 as a multifaceted candidate target in precision medicine. In Trends in immunology, 46, 219-228. doi:10.1016/j.it.2025.01.008. https://pubmed.ncbi.nlm.nih.gov/40044530/

9. Zhang, Ying, Chen, Chuangzhen, Liu, Zhaoyong, Hu, Wang, Lin, Zhixiong. 2022. PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p. In Journal of experimental & clinical cancer research : CR, 41, 111. doi:10.1186/s13046-022-02339-9. https://pubmed.ncbi.nlm.nih.gov/35346324/