Ifi44, an interferon-alfa inducible protein, is associated with the immune response to viral and bacterial infections, as well as autoimmune diseases. It is involved in interferon-related pathways, playing a part in the body's defense mechanisms and immune regulation [1,2].

In in vitro studies, Ifi44 inhibits HIV-1 replication by suppressing HIV-1 LTR promoter activity and affecting viral transcription. Depletion of endogenous Ifi44 in J-LAT cells induces reactivation of latent HIV-1, suggesting its role in maintaining HIV-1 latency [1]. In patients with rheumatoid arthritis (RA), Ifi44 is identified as a hub gene and an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection. It negatively regulates the IFN signaling pathway to promote viral replication and bacterial proliferation [2]. In head and neck squamous cell carcinoma (HNSCC), ACSL4 upregulates Ifi44 expression, promoting cell proliferation and invasiveness [3]. Also, in systemic lupus erythematosus (SLE) and its complication lupus nephritis (LN), Ifi44 is identified as a biomarker. Its expression in LN-affected kidneys is elevated, positively correlating with serum creatinine and SLEDAI, and inversely with serum complement C3 and initial eGFR [5,6]. In scallops, the expression pattern of Ifi44 genes responds to Vibrio challenge, which may be related to the higher resistance to Vibrio in hybrids [4].

In conclusion, Ifi44 plays a significant role in multiple biological processes, especially in the immune response to infections and in autoimmune diseases. Studies on Ifi44, including those potentially involving gene knockout models in relevant diseases like HIV-1 latency, RA-associated infections, HNSCC, SLE, and LN, have provided insights into its functions, helping to understand the underlying disease mechanisms and potentially guiding the development of new treatment strategies.

References:

1. Power, Derek, Santoso, Netty, Dieringer, Michael, Miao, Hongyu, Zhu, Jian. 2015. IFI44 suppresses HIV-1 LTR promoter activity and facilitates its latency. In Virology, 481, 142-50. doi:10.1016/j.virol.2015.02.046. https://pubmed.ncbi.nlm.nih.gov/25776761/

2. Zheng, Qingcong, Wang, Du, Lin, Rongjie, Lv, Qi, Wang, Wanming. 2022. IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA. In Frontiers in immunology, 13, 1013322. doi:10.3389/fimmu.2022.1013322. https://pubmed.ncbi.nlm.nih.gov/36189314/

3. Rupa, Darius, Chuang, Hao-Wen, Hu, Chung-En, Lee, Herng-Sheng, Yuan, Ta-Chun. 2024. ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells. In Cancer science, 115, 3026-3040. doi:10.1111/cas.16236. https://pubmed.ncbi.nlm.nih.gov/38989827/

4. Qu, Xiaoxu, Wang, Xia, Liu, Bo, Lu, Xia, Wang, Chunde. 2023. Potential roles of IFI44 genes in high resistance to Vibrio in hybrids of Argopecten scallops. In Fish & shellfish immunology, 135, 108702. doi:10.1016/j.fsi.2023.108702. https://pubmed.ncbi.nlm.nih.gov/36948367/

5. Tan, Yue, Wang, Xueyao, Zhang, Deyou, Yu, Jinyu, Wu, Hao. 2025. Determining IFI44 as a key lupus nephritis's biomarker through bioinformatics and immunohistochemistry. In Renal failure, 47, 2479575. doi:10.1080/0886022X.2025.2479575. https://pubmed.ncbi.nlm.nih.gov/40101924/

6. Shen, Lingling, Lan, Lan, Zhu, Tingting, Jiang, Hong, Chen, Jianghua. 2021. Identification and Validation of IFI44 as Key Biomarker in Lupus Nephritis. In Frontiers in medicine, 8, 762848. doi:10.3389/fmed.2021.762848. https://pubmed.ncbi.nlm.nih.gov/34760904/