Interferons belong to the large family of cytokines. Interferon is not a toxin designed to poison a key molecule in the cell. Instead, it is a message that is read by human cells. Interferon is one of a growing class of cytokines, proteins that deliver instructions from cell to cell. Normally, interferon, and the similar interleukins, mediate a continual conversation between cells about growth and defenses. Interferons are named after their ability to "interfere" with viral replication within host cells. Interferon was identified more than 50 years ago by Isaacs and Lindenmann during their studies of the phenomenon of viral interference, the ability of an active or inactivated virus to interfere with the growth of an unrelated virus. Today, more than 10 mammalian IFN species and numerous subspecies have been discovered, each with individual properties, but all having antiviral activity.
Interferons are currently classified into three groups: type I, type II and type III IFNs. The type I IFNs include all IFNαs, IFNβ, IFNε, IFNκ, IFNω and IFNν. Humans have 12 different IFNαs and a single IFNβ. Type I IFN genes are clustered on the human chromosome 9. Each subtype is encoded by its own gene and regulated by its own promoter, and none of them contain introns. The different IFNαs and IFNβ differ substantially in their specific antiviral activities and in the ratios of antiviral to antiproliferative activities. However, the molecular basis of these differences is not yet known. All type I IFNs bind to the same interferon alpha/beta receptor (IFNAR) which consists of two major subunits: IFNAR1 and IFNAR2c (the βL subunit).
There is only one class II IFN, IFNγ. Interferon gamma is produced by T lymphocytes when stimulated with antigens or mitogens. IFNγ binds to a distinct receptor, the interferon gamma receptor (IFNGR) consisting of the two subunits IFNGR1 (previously α chain) and IFNGR2 (previously β chain or accessory factor).
The more recently described type III IFNs IFNλ2, IFNλ3 and IFNλ1 are also known as IL28A, IL28B and IL29 respectively. The same as type I IFNs, they are also induced by viral infections. They signal through the IFN-λ receptor consisting of the IL-10R2 chain shared with the IL-10 receptor, and a unique IFNλ chain.
As with many other signaling proteins, interferons bring together two copies of a receptor to initiate the signal inside the cells. Interferons are relatively small proteins. Interferon-gamma is a dimeric protein, and it is composed of two identical chains, which intertwine extensively. Two copies of its receptor bind on either side of IFN-gamma. Interferon-alpha, on the other hand, is monomeric, composed of one chain, and two different receptor chains bind to different portions of the protein.
Alpha-interferons can modify immune function and gamma-interferon plays a role in defense. Apart from these duties in controlling abnormal growth, they also play supporting roles in the day-to-day maintenance of normal cellular growth levels. The messages are subtle and have different consequences when combined with the many messages passing from cell to cell. This complicates the use of interferon in therapy. Familiar hormones like insulin have simple, direct actions, so insulin is effective in replacement therapy. The artificial messages sent by interferon treatment, however, can be read incorrectly, leading to unwanted side effects. But in special cases, interferon can send just the right instructions, directing the immune system to destroy hairy cell leukemia cells or inhibiting the growth of blood vessels nourishing a Kaposi's sarcoma.
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