Distribution of Interferon-α2 Genes in Humans

In the normal course of a viral infection, human cells produce interferons (IFNs) as the first line of defense. These IFNs differ depending upon the cells and the nature of the infecting virus. Over the past 20 years it has become clear that there are many forms of IFNs produced. They can be grouped into four IFN families based upon their similarities and differences: alpha, beta, gamma, and omega IFNs. As shown in Table 1, only the alpha-interferon family contains more than one allelic form of IFN. Omega, beta, and gamma IFN families contain only one functional IFN species each. As many as 14 different nonallelic genes have been identified for IFN-α [1]. Thirteen of the 14 different species of IFN-α consist of 166 amino acids. Only one is shorter, by a single amino acid, i.e., IFN-α2. IFN-α2 lacks the aspartic acid in position 44 found in the mature IFN-α-proteins, making it only 165 amino acids in length. There are no introns in this family and two disulfide bonds are used to maintain the secondary structure of the molecule. All of the species in this IFN-α family share a very high degree of sequence homology [2]. The type I interferons, i.e., alpha-, beta-, and omega-IFN families are clustered on human chromosome 9. Interferon-γ, type II IFN, has been located on human chromosome 12. The extent of glycosylation of the proteins in the IFN-α family is low (i.e., ≤ 8% of the total protein weight) and appears to exist predomi-nantly as O-linked forms. One species of IFN-α has an N-linked asparagine site, i.e., IFN-α14, which was predicted from the cloned DNA sequence [3] and confirmed in the natural form of IFN-α14 [4].