IRF7
Description
The IRF7 (interferon regulatory factor 7) is a protein-coding gene located on chromosome 11.
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors. IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I interferon genes. In particular, IRF7 regulates many interferon-alpha genes. Constitutive expression of IRF7 is largely restricted to lymphoid tissue, largely plasmacytoid dendritic cells, whereas IRF7 is inducible in many tissues. Multiple IRF7 transcript variants have been identified, although the functional consequences of these have not yet been established. The IRF7 pathway was shown to be silenced in some metastatic breast cancer cell lines, which may help the cells avoid the host immune response. Restoring IRF7 to these cell lines reduced metastases and increased host survival time in animal models. The IRF7 gene and product were shown to be defective in a patient with severe susceptibility to H1N1 influenza, while susceptibility to other viral diseases such as CMV, RSV, and parainfluenza was unaffected. IRF7 has been shown to interact with IRF3.
IRF7 is a key regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. It 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. IRF7 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. It induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner. IRF7 is 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. It 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. IRF7 can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. It binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. IRF7 can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.
IRF7 is also known as IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C, IRF7H.
