IRF7

IRF7 stands for "Interferon Regulatory Factor 7". IRF7, the interferon regulatory factor 7, is 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 interferon beta chain genes. The inducible expression of IRF7 is largely restricted to lymphoid tissue. IRF7 is encoded by the gene of the same name.

IRF7 plays an important role in the innate immune response against DNA and RNA viruses. It is an important transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a crucial role in the innate immune response against DNA and RNA viruses. Furthermore, the interferon regulatory factor 7 encoded by this gene 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. It can efficiently activate both IFN-beta (IFNB) and IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway.

Interferon regulatory factor 7 is required in both the early and late phases of IFN gene induction. It exists in an inactive form in the cytoplasm of uninfected cells and is phosphorylated and upregulated by the kinases IKBKE and TBK1 following viral infection, double-stranded RNA (dsRNA) or Toll-like receptor (TLR) signaling. This results in a conformational change that leads to its dimerization and nuclear localization, where it can activate transcription of type I IFN and ISG genes together with other coactivators. Can activate various gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.

In dendritic cells, macrophages or keratinocytes, IRF7 can indirectly activate other signaling pathways such as the cGAS-STING pathway through UV-induced signaling pathways (UV-induced DNA damage, e.g. on keratinocytes), which leads to the production of type I infertons.

Diseases associated with IRF7 include:

• autosomal recessive immunodeficiency 39 (Immunodeficiency 39; OMIM: 616345)
• and
• predisposition to severe viral infections due to IRF7 protein deficiency.

1. Ciancanelli MJ et al. (2015) Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science 348: 448-453.
2. Honda K et al. (2005) IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434: 772-777.