At least three human type alpha interferons: structure of alpha 2.

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• Human leukocyte-derived complementary DNA (cDNA) Hif-2h directs the synthesis of interferon-alpha 1 (IFN-alpha 1) with interferon (IFN) activity.
• Interferons are crucial proteins involved in the immune response against pathogens.

Purpose of the Study:

• To describe a second IFN cDNA, Hif-SN206, that elicits the synthesis of a biologically active interferon, IFN-alpha 2.
• To compare the biological activity and sequence characteristics of IFN-alpha 1 and IFN-alpha 2.
• To investigate the genetic basis of human interferon-alpha production.

Main Methods:

• Complementary DNA (cDNA) sequencing to determine the genetic sequences of Hif-2h and Hif-SN206.
• Expression in Escherichia coli to produce interferon polypeptides.
• Biological assays to measure interferon activity on human and bovine cells.
• Nucleotide and amino acid sequence analysis to compare IFN-alpha 1 and IFN-alpha 2.
• Genomic DNA studies to assess the number of interferon-related genes.

Main Results:

• A second active interferon, IFN-alpha 2, was synthesized from the Hif-SN206 cDNA.
• IFN-alpha 2 showed twice the activity on human cells compared to bovine cells.
• IFN-alpha 1 exhibited 10-20 times greater activity on bovine cells than on human cells.
• The messenger RNAs for IFN-alpha 1 and IFN-alpha 2 differ in length and 20% of nucleotides.
• The mature IFN polypeptides differ in 17% of their amino acids.
• Both IFN-alpha 1 and IFN-alpha 2 are distinct from previously described lymphoblastoid IFNs.
• Genomic DNA analysis indicates at least eight interferon-related genes in humans.

Conclusions:

• At least three different IFN-alpha genes are expressed in humans.
• The existence of multiple interferon-alpha genes contributes to the diversity of interferon functions and activities.
• Further research into human interferon genes is warranted to fully understand their roles in immunity.