The Role of Three Domains in the Biological Activity of Human Interferon-α

ABSTRACT Earlier studies showed that minor differences in primary structure among the interferon-α (IFN-α) protein family are reflected in their potency in selected biological assays. These studies have been extended and results from assays of antiviral, growth inhibitory and 2′,5′-oligoadenylate (2-5A) synthetase activities indicate that the various novel hybrid and analog species are differentially biologically active. Overall these observations suggest a correlation between predicted secondary structure characteristics, receptor binding affinity, and 2-5A synthetase, antiviral and growth inhibitory activities. Studies with a consensus IFN-α analog particularly implicated the region around residues 78 and 79 as influencing antiviral activity. Neutralization experiments with a monoclonal antibody directed against a conserved region from residues 113 to 149 indicated that although this region of the IFN-α molecule may be important for antiviral activity, altering residues at sites removed from this region...