Ask about this productRelated genes to: IFIT3 Blocking Peptide
- Gene:
- IFIT3 NIH gene
- Name:
- interferon induced protein with tetratricopeptide repeats 3
- Previous symbol:
- IFIT4
- Synonyms:
- ISG60, RIG-G, CIG-49, IFI60, GARG-49, IRG2
- Chromosome:
- 10q23.31
- Locus Type:
- gene with protein product
- Date approved:
- 1998-08-13
- Date modifiied:
- 2015-11-27
Related products to: IFIT3 Blocking Peptide
Related articles to: IFIT3 Blocking Peptide
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems. In SLE, T-cell subsets are closely associated with autoimmunity and organ inflammation. Detecting T-cell exhaustion (TEX)-related biomarkers is crucial for early SLE diagnosis and offers new insights into disease mechanisms. Transcriptomic data for SLE were collected from public databases, and TEX-related genes were obtained from the literature. Biomarkers were identified using analyses such as differential expression analysis and machine learning algorithms. The potential mechanisms of action of these biomarkers were further investigated, including nomogram construction, gene set enrichment analysis, immune microenvironment analysis, molecular regulatory network analysis, molecular docking, and reverse transcription-quantitative polymerase chain reaction validation. IFIT3, IFIH1, CXCL10, and STAT2 were identified as biomarkers. The nomogram demonstrated good predictive performance. These biomarkers were mainly involved in biological processes such as ribosome biogenesis and negative regulation of viral genome replication. Four significantly different immune cell types were identified, including monocytes and resting memory CD4 T cells. The biomarkers were found to be regulated by several transcription factors and microRNAs. Furthermore, the 4 biomarkers exhibited high binding affinity for several drugs; in particular, the binding energy of STAT2 with bisphenol A was -7.0 kcal/mol. Finally, reverse transcription-quantitative polymerase chain reaction results showed that all 4 biomarkers were significantly upregulated in SLE patients. In summary, this study identified TEX-related biomarkers in SLE, which may have important clinical implications for the diagnosis and treatment of SLE. - Source: PubMed
Yang LanqingGao WeiYang LuluLiu Xingyu - African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a fatal and highly contagious disease, resulting in enormous losses to the global swine industry. No licensed vaccines or effective therapeutics are currently available to control ASFV infection. Interferons (IFNs) serve as key mediators of host antiviral immunity by inducing interferon-stimulated genes (ISGs), but the specific mechanisms by which individual ISGs restrict ASFV replication remain unclear. Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3, also called ISG60) has been shown to exhibit antiviral activity against various viruses, but its role in ASFV infection has not been previously studied. Here, we used porcine alveolar macrophages (PAMs), the primary target cells of ASFV, to investigate IFIT3's function in ASFV replication. We found that overexpression of IFIT3 inhibited ASFV replication, while its knockdown enhanced viral propagation. Mechanistically, IFIT3 directly blocked ASFV adsorption to host cells, thereby suppressing all subsequent stages of the viral cycle. IFIT3 also specifically interacted with ASFV F334L, an early viral gene product that encodes the small subunit of ribonucleotide reductase, a key enzyme for viral DNA synthesis. Additionally, IFIT3 positively regulated the STAT1/TBK1/IRF3 signaling axis: its overexpression increased phosphorylation of TBK1 and IRF3, as well as the protein level of STAT1, while IFIT3 knockdown attenuated activation of these molecules. Transcriptomic analysis of IFIT3-knockout PAMs revealed significant suppression of innate immune pathways, including type I interferon, JAK-STAT, and RIG-I-like receptor pathways, along with downregulated expression of core antiviral molecules such as ISG15, MX1, and STAT1. Conversely, pathways related to viral adsorption, endocytosis, and cytoskeleton were activated, and pathways involved in protein translation initiation, endoplasmic reticulum stress, and autophagy were dysregulated, creating a favorable intracellular environment for ASFV replication. In conclusion, IFIT3 restricts ASFV replication possibly by inhibiting viral adsorption and promoting innate immune signaling, identifying it as a potential therapeutic target against ASFV. This study's limitation is its in vitro PAM model; future work will validate IFIT3's role in vivo and develop targeted inhibitors. - Source: PubMed
Publication date: 2026/05/17
Wang Wen-LiHan Deng-WuYang XingShi Xi-JuanShen Ye-ShengTian Shu-YaoChang Zhi-HaiZhang Deng-JiZeng Qiao-YingBao Shi-JunZheng Hai-XueMao Ruo-Qing - Oncolytic virus M1 is a promising anticancer agent; however, its therapeutic efficacy is often limited by insufficient intratumoral viral replication and host antiviral immunity. Sirolimus, an mTOR inhibitor widely used in transplantation immunosuppression, has demonstrated potential to modulate antiviral responses. This study investigates whether sirolimus potentiates the efficacy of M1 virotherapy and elucidates the underlying mechanisms. Sirolimus significantly enhanced the antitumor efficacy of M1 virus in murine prostate cancer and liver cancer models, leading to reduced tumor growth. This synergistic effect remained evident in CD8⁺ T cell-depleted mice, indicating that the therapeutic benefit is independent of adaptive cytotoxic immunity. Mechanistically, sirolimus markedly increased M1 viral replication in tumor tissues, accompanied by enhanced tumor cell-cycle arrest and apoptosis. Notably, sirolimus selectively amplified viral load within tumors but not in normal organs, demonstrating tumor-specific viral enrichment and safety. Further analyses revealed that this increase in intratumoral virus was driven by mTOR pathway inhibition rather than alterations in macrophage or NK cell populations. Transcriptomic profiling and molecular validation indicated that sirolimus-mediated mTOR suppression downregulated key type I interferon-stimulated genes (Ifitm1, Stat1, Ifit3), thereby attenuating intrinsic antiviral defenses and facilitating viral amplification. In summary, sirolimus potentiates M1 oncolytic virotherapy by selectively enhancing viral replication in tumors via mTOR inhibition and suppression of type I interferon signaling, independent of CD8⁺ T cell-mediated immunity. These findings establish a mechanistic rationale for combining mTOR inhibitors with oncolytic viruses to achieve dual benefits of enhanced viral oncolysis and controlled immunosuppression, with translational relevance for cancer patients requiring long-term immunosuppressive therapy. - Source: PubMed
Publication date: 2026/05/25
Chen Jie-HongLi Hong-HuiChen Chao-XinYan Cai-XinLiang Xuan-MingGuo CuiHan YuTang Yun-HuaLiu YingCai JingLin YuanLiang Jian-KaiHu JunYan Guang-MeiLi Jing-JieZhu Wen-Bo - Effective host survival during viral infection depends on the ability to discriminate endogenous messenger RNA from pathogenic RNA species. Interferon-induced proteins with tetratricopeptide repeats (IFITs) constitute a central component of this defence system, functioning as specialised cytosolic RNA surveillance proteins that detect molecular features characteristic of non-self transcripts. This review examines the dynamic evolutionary interplay between IFIT-mediated antiviral restriction and viral evasion strategies. IFIT proteins recognise defined chemical and structural determinants at the RNA 5' terminus-including 5'-triphosphorylated ends and the absence of 2'-O-methylation-and sequester such transcripts to inhibit viral translation. In response, RNA viruses have evolved sophisticated evasion strategies, including the encoding or acquisition of 2'-O-methyltransferases, exploitation of host cap-modifying enzymes, and cap-snatching mechanisms that generate host-like cap 1 and m⁶Am signatures to evade immune recognition. Beyond the canonical antiviral roles attributed to IFIT1 and IFIT5, accumulating evidence indicates that IFIT2 and IFIT3 function as critical regulatory components within IFIT complexes, stabilising protein-protein interactions, modulating RNA-binding affinity, and influencing downstream signalling pathways. Collectively, these concepts position IFIT proteins as RNA surveillance proteins and regulatory scaffolds within innate immunity. We propose that future antiviral strategies should focus on unmasking viral RNA, thereby restoring its detection by the host innate immune system. - Source: PubMed
Publication date: 2026/05/22
González-Hilario SaulZepeda-Cendejas PaulinaCibrian-Segura Marcela EsmeraldaAvila-Bonilla Rodolfo Gamaliel - Bladder cancer (BC), particularly muscle-invasive or metastatic disease, remains a major clinical challenge despite advances in immunotherapy. In this study, five candidate small molecules were screened, and cryptotanshinone (CTS) was identified as the most promising compound. Using BC cell lines and bladder tumor organoids, we evaluated the effects of CTS on proliferation, migration, apoptosis, and organoid growth. Transcriptomic sequencing of bladder tumor organoids, combined with protein-protein interaction analysis and public databases (TCGA-BLCA, TIMER, and TISIDB), was used to characterize CTS-associated molecular features. Integrative analyses identified IFIT1, IFIT2, and IFIT3 as representative interferon-stimulated candidate genes associated with BC progression, prognosis, immune infiltration, and PD-1/PD-L1 expression. These findings were supported by qRT-PCR and Western blot analyses showing reduced IFIT1/2/3 expression at both mRNA and protein levels following CTS treatment. Molecular docking suggested potential associations between CTS and interferon-related signaling proteins. Consistently, CTS reduced TBK1 and STAT1 phosphorylation, providing preliminary experimental support for its association with interferon-related signaling modulation. Collectively, CTS exerts growth-inhibitory effects and is associated with tumor cell-intrinsic interferon-related transcriptional and signaling changes in BC models, providing a basis for further investigation as a small-molecule candidate for BC. - Source: PubMed
Publication date: 2026/05/13
Yang MengniLi ShanLi RuiDong YuZhou MengtingZhao JunningLiu MiaoTan Ruirong