Recombinant human IFN-α family

Type I interferons (IFN) include the IFN-α family, IFN-β, IFN-ε, IFN-κ and IFN-ω. IFN-αs are important anti-viral cytokines that also have anti-proliferative and immuno-modulatory functions. The human IFN-α family comprises 13 genes encoding 12 proteins, with IFN-α13 being identical to IFN-α1. All IFN-αs bind to a common heterodimer receptor IFNAR1/IFNAR2. The ternary complex signals through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathway, inducing the formation of the ISGF3 transcriptional complex (STAT1/STAT2/IRF9). ISGF3 binds to IFN-stimulated response elements (ISRE) in the promoter regions of numerous IFN-stimulated genes (ISGs) [1].

Human IFN-α genes have evolved under strong selective pressure, suggesting a non-redundant role between IFN-α subtypes [2]. Although most studies have focused on IFN-α2 and IFN-α8, a consensus model for all IFN-αs has emerged depending on the affinity of a particular IFN-α subtype for IFNAR. Low affinity IFN-α subtypes signal strictly through ISGF3 and induce robust ISGs, such as PKR, ISG56, and IFI16, which display anti-viral functions. Conversely, high affinity IFN-α subtypes signal through ISGF3 and other factors, which activate “tunable” ISGs” such as CXCL10, IL-8, and ISG15, that induce anti-proliferative and immuno-modulatory functions [3]. IFN-α8, IFN-α10 and IFN-α14 have been identified as the most potent inducers of ISGs, while IFN-α1 is the weakest [4].

References:

1. Schreiber G. 2017. The molecular basis for differential type I interferon signaling. J. Biol. Chem. 292:7285-94.
2. Manry J. et al., 2011. Evolutionary genetic dissection of human interferons. J. Exp. Med. 208:2747-59.
3. Levin D. et al., 2014. Multifaceted activities of type I interferon are revealed by a receptor antagonist. Sci. Signal. 7(327). ra50.
4. Kurunganti S. et al., 2014. Production and characterization of thirteen human type-I interferon-α subtypes. Protein Expr. Purif. 103: 75-83.