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Type I Interferons

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Are all Type I IFNs created equal?


Type I Interferons were the first cytokines to be discovered. They are a family of homologous cytokines originally identified for their antiviral activity but have also been shown to have both anti-proliferative and immunomodulatory activities. In humans and mice they are encoded by an intronless multigene family clustered on human chromosome 9 and murine chromosome 4 respectively.


Also in both species there are multiple Interferon-Alpha (IFN-a) genes and one Interferon-Beta (IFN-b) gene. Other Type I Interferon genes described include the Interferon-Omega (IFN-w) gene, murine limitin gene, as well as the human/murine Interferon-Epilson, Interferon-Kappa, and Interferon-Tau (IFN-e, IFN-k, and IFN-t).

In humans, at least 13 IFN-a are transcribed. Two of these genes (IFNA1 and IFNA13) are identical in coding sequences and give rise to a single protein species. The coding sequences of the rest of human IFN-a genes diverge up to 8% and give rise to 12 protein subtypes. Similarly, one IFN-b and 13 IFN-a genes have been described in the mouse. Table below lists the common Human IFN-a subtypes. It is important to note that human IFN-a nomenclature is different from murine IFN-a nomenclature.


All IFN-a subtypes and IFN-b are structurally similar and share a common cell surface receptor, which is composed of two chains designated as IFNAR1 and IFNAR2. In humans, only one IFN-a subtype is N-glycosylated and a few IFN-a species have been shown to be O-glycosylated. In the mouse, nearly all of the IFN-a species are N-glycosylated. Globally, glycosylated IFN-a subtypes do not differ from non-glycosylated subtypes in terms of their biological activities. A variety of studies have suggested that these IFN-a subtypes possess overlapping but also unique sets of distinctive biological activities as well as differential expression.

 

Of Mice and Men


The biological significance of the expression of so many different IFN-a subtypes has yet to be determined. However, reports suggest that they show quantitatively distinct anti-viral, anti-proliferative, and killer cell-stimulatory activities. It is therefore of importance for researchers to characterize and study these IFN-a subtypes and their possible post-translational modifications.

 

Do you know what’s your type?

Although all Type I IFNs, including all IFN-a subtypes, bind to a common receptor (composed of two subunits IFNAR-1 and IFNAR-2), the variations in biological activities among IFN-a subtypes suggest that receptor affinities may not be the only explanation for the diverse effects of IFN-a subtypes. It may be possible that IFN-a subtype-specific signaling pathways contribute to the differences between IFN-a subtypes. Elucidating the functional significances of various IFN-a subtypes not only can lead to a better understanding on the role interferons have in the immune system, but also to the refinement of current interferon based therapeutic applications.
In collaboration with PBL InterferonSource, tebu-bio offers the largest selection of interferons, including alpha subtypes from different animal species and assay kits to analyze them.

 


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