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The 3D structure of human IFN-β

Human type I interferons comprise a vast and growing group of IFN proteins.

All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains.

Homologous molecules to type I IFNs are found in many species, including most mammals, and some have been identified in birds, reptiles, amphibians and fish species.^[1]

[edit] Types

The types are designated IFN-α (alpha), IFN-β (beta), IFN-κ (kappa), IFN-δ (delta), IFN-ε (epsilon), IFN-τ (tau), IFN-ω (omega), and IFN-ζ (zeta, also known as limitin). ^[2].^[3]

[edit] IFN-α

The IFN-α proteins are produced by leukocytes. They are mainly involved in innate immune response against viral infection. They come in 13 subtypes that are called IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21. These genes for these IFN-α molecules are found together in a cluster on chromosome 9.

IFN-α is also made synthetically as medication. Types are:

• Pegylated interferon alfa-2a
• Pegylated interferon alfa-2b

[edit] IFN-β

The IFN-b proteins are produced by fibroblast. They have antiviral activity which mainly involved in innate immune response. Two types of IFN-β have been described, IFN-β1 (IFNB1) and IFN-β3 (IFNB3)^[4] (a gene designated IFN-β2 is actually IL-6).

[edit] IFN-ε, –κ, -τ, and –ζ

IFN-ε, –κ, -τ, and –ζ appear, at this time, to come in a single isoform in humans, IFNK.

[edit] IFN-ω

IFN-ω, although having only one functional form described to date (IFNW1), has several pseudogenes: IFNWP2, IFNWP4, IFNWP5, IFNWP9, IFNWP15, IFNWP18, and IFNWP19.

[edit] Sources and functions

IFN-α and IFN-β are secreted by many cell types including lymphocytes (NK cells, B-cells and T-cells), macrophages, fibroblasts, endothelial cells, osteoblasts and others. They stimulate both macrophages and NK cells to elicit an anti-viral response, and are also active against tumors.

IFN-ω is released by leukocytes at the site of viral infection or tumors.

IFN-α acts as a pyrogenic factor by altering the activity of thermosensitive neurons in the hypothalamus thus causing fever. It does this by binding to opioid receptors and eliciting the release of prostaglandin-E₂ (PGE₂).

A similar mechanism is used by IFN-α to reduce pain; IFN-α interacts with the μ-opioid receptor to act as an analgesic.^[5]

[edit] References

1. ^ Schultz et al., The interferon system of non-mammalian vertebrates. Developmental and Comparative Immunology, Volume 28, pages 499-508.
2. ^ Oritani and Tomiyama, Interferon-ζ/limitin: Novel type I Interferon that displays a narrow range of biological activity. International journal of hematology, 2004, Volume 80, pages 325-331 .
3. ^ Hardy et al., Characterization of the type I interferon locus and identification of novel genes. Genomics, 2004, Volume 84 pages 331-345.
4. ^ Todd and Naylor, New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene. Somat. Cell. Mol. Genet. 1992 Volume 18, pages 381-5.
5. ^ Wang et al., Fever of recombinant human interferon-alpha is mediated by opioid domain interaction with opioid receptor inducing prostaglandin E2. J Neuroimmunol. 2004 Nov;156(1-2):107-12.

[edit] External links

• MeSH Interferon+Type+I