The IFN-alpha family represents a family of related and homologous proteins, each exhibiting a unique activity profile. Each IFN-a species seems to exhibit a distinct profile of activities [antiviral, antiproliferative, and stimulation of cytotoxic activities of natural killer (NK) cells and T cells]

For the most part, the IFN-alpha species are not glycosylated, although some contain carbohydrates.

Within each subtype of mammalian Type I IFN, there is additional variability in gene duplication. The IFN-a genes are duplicated to a much greater extent than any other subtype of Type I IFN. This observation in conjunction with the observation that the IFN-a subtypes generally possess the highest specific antiviral activity imply that physiologically, the body likely uses IFN-a as the primary antiviral defense protein and that the major function of IFN-a is defense.

=Structure=

STRUCTURE: The Type I IFNs consist of five a-helices (labeled A–E) which are linked by one overhand loop (AB loop) and three shorter segments (BC, CD, and DE loops). Helices A, B, C, and E are arranged in an antiparallel fashion to form a left-handed four-helix bundle. The AB loop contains short segments of 3_10 helix and is best described in three segments labeled AB1, AB2, and AB3. In all Type I IFNs, the AB1 loop encircles and is linked to helix E by a disulfide bond. An additional disulfide bond is observed in most IFN-a subtypes but not IFN-b, which connects the N-terminus of the molecule to helix C. The AB loop is critical for high-affinity IFNAR2 binding and suggest that sequence differences in this region may hold the key to differences in biological activity between the different IFN-a subtypes.

IFNa2 contain 165 amino acids; according to circular dichroism measurements ~68% of the residues adopt helical conformation.INFa2 is composed of five a-helices, labeled A–E, linked by one long overhand connection (AB loop) and three short segments (BC, CD and DE loops). The topology of the molecule resembles the classical up-up-down-down four-helixbundle motif; helices A, B, C, and E comprise the helix bundle.

=Receptors=

The IFNs and IFN-like molecules signal through the Jak-Stat pathway. The receptor for the Type I IFNs consists of two chains, IFN-aR1 and IFN-aR2c. The ligand INF-alpha is a monomer that binds to the two-chain complex of IFN-aR1 and INF-aR2c.

Type I IFNs are stable at acidic pH (pH 2) and are represented by two major subtypes, the fibroblast or beta interferon (IFN-b) and the leukocyte or alpha family of interferons (IFN-a).

The only known interferon of type II is IFN-g, which is produced exclusively by lymphocytes.

Interferon is species-specific: the substance prepared from infected eggs protected only chicken cells from virus infection, while the similar substance prepared from mice protected only mouse cells.

Produced by many cells in the human body by a receptor dependent feedback mechanism.

Interferons are part of the "first-wave" immune response of the innate immune system, acting within hours, whereas antibody production takes days.

In general, exposure of human cells to viruses or double stranded RNAs induces the production of IFN-a, IFN-b, and IFN-o species.

The IFNs were the first of the proteins we now recognize as members of the Class II cytokine family.