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Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression). [1] Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF-element (IRF-E) motifs, which is located upstream of the interferon genes. [2]
IRF3 is a member of the interferon regulatory transcription factor (IRF) family. [5] IRF3 was originally discovered as a homolog of IRF1 and IRF2.IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites. [6]
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[27] [28] Reducing IFN-α activity may prevent signaling via STAT1, STAT2, or IRF9 (as with JEV infection) or through the JAK-STAT pathway (as with DEN-2 infection). [26] Several poxviruses encode soluble IFN receptor homologs—like the B18R protein of the vaccinia virus—that bind to and prevent IFN interacting with its cellular receptor ...
IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation. [11] The IRF family can also initiate the JAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK. [12] IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals. [13]
Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially described as a transcription factor able to activate expression of the cytokine Interferon beta, [6] IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes.
The expression of pattern recognition receptors like a TLR or common signaling proteins like those found in the JAK-STAT pathway may be up regulated by interferons, making the cell more sensitive to interferons. [10] As such a large portion of the human genome is associated with interferon ISG have a broad range of functions.
Activation of various innate immune signaling pathways (TLR3, TLR4, TLR7, TLR8, TLR9, cGAS, RIG-I, MDA-5) leads to the rapid induction of type I IFNs due to their (mostly) intronless gene structure. [3] [4] The regulatory elements upstream of type I IFN genes differ, allowing differential transcription of type I IFNs in response to stimuli. [5]