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IFNs

Monday 9 January 2006

The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis.

Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity.

Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics.

Interferons may be regarded as polypeptide hormones because of their role in communicating from cell to cell a specific set of instructions that lead to a wide variety of effects.

Viruses induce type I interferon, subdivided into alpha-interferon (MIM.147660), produced by leukocytes or lymphoblastoid cells, and beta-interferon (MIM.147640), produced by fibroblasts.

Mitogens and antigenic stimuli induce in lymphocytes type II, immune, or gamma-interferon (MIM.147570).

The biologic effects of human interferons, including increment of histocompatibility antigens, are mediated through species-specific receptors. Human interferons are not active, for example, in mouse cells.

The human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2 (MIM.147569). IFNGR1 is the ligand-binding subunit.

Types

There are three major classes of interferons that have been described for humans according to the type of receptor through which they signal:

- interferons type 1: 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. The type I interferons present in humans are IFN-α ((IFNA), IFN-β (IFNB) and IFN-ω (IFNW).
- interferons type 2: Binds to IFNGR. In humans, this is IFN-γ (IFNG).
- interferons type 3: Signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12).

Members

- interferons type 1

INFA INFB

- interferons type 2

INFG

References

- Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, Foster GR, Stark GR. Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007 Dec;6(12):975-90. PMID: 18049472

- Jefferies CA, Fitzgerald KA. Interferon gene regulation: not all roads lead to Tolls. Trends Mol Med. 2005 Sep;11(9):403-11. PMID: 16095970