Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.

1. cFLIP appears to bind to IKKalpha to prevent IKKalpha from phosphorylating and activating IRF7. PMID: 29222334
2. our results suggest that expression of IRF7 is one of the metastatic effectors of LMP1 signalling in Epstein-Barr virus-associated nasopharyngeal cancer PMID: 28712115
3. Hypomethylation of the IRF7 promoter might play a role in systemic sclerosis pathogenesis, probably through promoting the IRF7 expression in PBMCs of patients with SSc. PMID: 28952189
4. Results showed that INF-lambda serum concentration was increased in Alzheimer's disease (AD) and mild cognitive impairment (MCI) carrying the IFNL3 T allele compared to healthy controls (HC). Anti-HSV-1 Ab titers were higher in AD and MCI individuals carrying the IRF7 AA genotype compared to HC. IFNL3 rs12979860 and IRF7 rs6598008 polymorphisms may modulate immune responses against HSV-1 via their effect on the IFN-lam... PMID: 28984602
5. IRF7 plays a role in reducing bone metastasis of prostate cancer by IFN-beta-mediated NK activity. PMID: 27733217
6. The MYC is shown to be recruited to the IRF7 promoter region through interaction with nuclear receptor corepressor 2/histone deacetylase 3 for its repression. PMID: 27630164
7. S100A9 knockdown almost completely abrogated the effects of IRF7 deletion on granulocytic myeloid-derived suppressor cells (G-MDSC) development and tumor metastasis. IRF7 represents a novel regulator for G-MDSC development in cancer and may have predictive value for tumor progression. PMID: 28092673
8. the transcription factor NFATC3 binds to IRF7 and functions synergistically to enhance IRF7-mediated IFN expression in Plasmacytoid dendritic cells. PMID: 27697837
9. We show that IRF-7 siRNA knockdown enhanced LPS-induced IL-10 production in human monocyte-derived macrophages, and USP-18 overexpression attenuated LPS-induced production of IL-10 in RAW264.7 cells. Quantitative PCR confirmed upregulation of USP18, USP41, IL10, and IRF7. An independent cohort confirmed LPS induction of USP41 and IL10 genes PMID: 27434537
10. KSHV-encoded viral IRF4 interacts with the host IRF7 and inhibits interferon-alpha production. PMID: 28342865
11. The adaptor molecule RAIDD coordinates IKKepsilon and IRF7 interaction to ensure efficient expression of type I interferon. PMID: 27606466
12. Bcl6, by interacting with the co-factors NcoR2 and HDAC3, plays a pivotal role in controlling IRF7 induction and antiviral signaling priming. PMID: 26728228
13. Human IRF7 was shown to be essential for interferon type I-dependent protective immunity against primary influenza. (Review) PMID: 26761402
14. The IRF7 GG genotype associate with Cognitive Decline and Dementia. PMID: 25835418
15. IRF7 cleavage by the 3C protease of enterovirus D68 abrogated its capacity to activate type I interferon expression and limit virus replication. PMID: 26608321
16. Interferon regulatory factor 7 (IRF7) is a direct target of miR-762 and overexpression of miR-762 reduced expression of IRF7. PMID: 26597380
17. Data indicate that the type-I interferon master regulator gene interferon regulatory factor 7 (IRF7) is only hypomethylated in lupus patients with renal involvement. PMID: 26005050
18. our results indicate that IRF7 promotes glioma cell invasion and both chemoresistance and radioresistance through AGO2 inhibition PMID: 25680411
19. The interaction between AIP and IRF7 is enhanced upon virus infection, and AIP potently inhibits IRF7-induced type I IFN (IFN-alpha/beta) production. PMID: 25911105
20. Authors found that knockdown of IRF7 leads to growth inhibition of Epstein-Barr virus-transformed cells, and restoration of IRF7 by exogenous plasmid correlates with growth recovery of the viral transformed cells. PMID: 25300801
21. In TSC2-deficient angiomyolipoma patient cells, IRF7 is a pivotal factor in the Rheb/mTOR pathway. PMID: 25476905
22. These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. PMID: 25814066
23. Authors conclude that paramyxoviruses trigger the DNA damage response, a pathway required for MSK1 activation of phospho Ser 276 RelA formation to trigger the IRF7-RIG-I amplification loop necessary for mucosal interferon production. PMID: 25520509
24. phosphorylation-mediated IRF7 transactivation is controlled by a tripod-helix structure. PMID: 25225665
25. Data indicate that knockdown of IRF-7 expression almost completely diminished the enhancing effect of TLR9 signaling on Foxp3 expression, suggesting that IRF-7 is a downstream molecule of TLR9 signaling. PMID: 23490285
26. In over 800 breast cancer patients, high expression of Irf7-regulated genes in primary tumors was associated with prolonged bone metastasis-free survival. PMID: 22820642
27. Tat interaction with the 2 MAPKK and IRF7 promoters in HIV-1-infected cells and the resulting persistent activation of interferon-stimulated genes, which include inflammatory cytokines and chemokines, can contribute to the increased immune activation. PMID: 23535064
28. In the present study, the authors report that enterovirus 71 downregulates IRF7 through the 3C protein, which inhibits the function of IRF7. PMID: 23175366
29. The major allele of a nonsynonymous polymorphism, rs1131665 (412Q) in IRF7, confers elevated activation of IRF-7 and predisposes to the development of systemic lupus erythematosus in multiple ethnic groups. PMID: 21360504
30. None of the IRF7 polymorphisms was associated with systemic lupus erythematosus. PMID: 22433914
31. phosphorylation of IRF7 on Ser477 and Ser479 by IKKepsilon or TBK1 is inhibited by KSHV ORF45 PMID: 22787218
32. discuss the association of IRF7 and SLE based on recent understandings to render more information about the mechanisms of IRF7 might perform in PMID: 22455868
33. Reconstruction of the wiring diagram of the modules revealed the presence of hyperconnected hub nodes, most notably interferon regulatory factor 7, which was identified as a major hub linking interferon-mediated antiviral responses. PMID: 22112518
34. IRF7 single nucleotide polymorphism rs1061501 TT genotype and T allele are enriched in Taiwanese patients with systemic lupus erythematosus (SLE) and seem to be associated with an increased risk of developing SLE. PMID: 21632682
35. Vesicular stomatitis Indiana virus-activated IRF7 upregulates expression of the BST2 gene independently of interferon signaling. PMID: 22301143
36. TRAF6 can regulate HIV-1 production and expression of IRF7 promotes HIV-1 replication. PMID: 22140520
37. IRF7 region is an anticentromere autoantibody propensity locus in systemic sclerosis PMID: 21926187
38. Vaccinia virus protein C6 inhibits the activation of IRF7 by TBK1- and IKKepsilon-dependent pathways. PMID: 21931555
39. The ubiquitin E3 ligase activity of tripartite motif-containing (TRIM)28 protein is specific to IRF7. PMID: 21940674
40. Cigarette smoke suppresses key plasmacytoid dendritic cells functions upon viral infection by a mechanism that involves downregulation of TLR7 expression and decreased activation of IRF-7. PMID: 21435390
41. Study did not find signi fi cant relationships between rs4963128 or rs2246614 of IRF7/KIAA1542 and the risk of systemic lupus erythematosus, differing from a previous study of European women PMID: 21167895
42. analysis of IFN-stimulated response elements (ISREs) that bind to both the IFN-stimulated gene factor 3 (ISGF3) as well as to IFN response factor 7 (IRF7) PMID: 20943654
43. ORF45 may maintain the IRF-7 molecule in the closed form and prevent it from being activated in response to viral infection PMID: 20980251
44. These findings demonstrate that the lysine residues of IRF-7 play important roles in mediating IFN synthesis and modulating viral lytic replication. PMID: 20844090
45. IRF-7-induced HPV8 transcription in primary keterinocytes. PMID: 20980500
46. interferon regulatory factor 7C has dual roles in Epstein-Barr virus-mediated lymphocyte transformation PMID: 20209099
47. HCV infection enhances STAT1 expression but impairs nuclear translocation of IRF-7 and its downstream molecules. These impairments in the IFN-alpha signaling pathway may, in part, be responsible for establishment of chronic HCV infection. PMID: 20810735
48. Results suggest that Ro52-mediated ubiquitination promotes the degradation of IRF7 following TLR7 and TLR9 stimulation. PMID: 20668674
49. EBV infection correlated with a blockage in the activation of JAK/STAT pathway members and affected the level of phosphorylated IFN regulatory factor 7 (IRF7). PMID: 20689596
50. Smokers after infection with influenza is associated with reduced expression of IRF7 in nasal epithelial cells. PMID: 19880818

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Nucleus. Cytoplasm. Note=The phosphorylated and active form accumulates selectively in the nucleus.

IRF family

Expressed predominantly in spleen, thymus and peripheral blood leukocytes.

HGNC: 6122

OMIM: 605047

KEGG: hsa:3665

STRING: 9606.ENSP00000329411

UniGene: Hs.166120