Interferon-alpha/beta-receptor interactions: A complex story unfolding

The Type I interferons (IFN-alpha/beta) exhibit pleiotropic biological activities. Notably, the different IFN subtypes activate the same cell surface receptor complex to mediate variable responses. Accumulating evidence suggests that distinct differences in critical amino acid residues among the different IFN-alphas and IFN-beta determine the nature of the ligand-receptor interaction and the subsequent responses. This review focuses on IFN-receptor interactions, the key residues involved in this interaction and the potential for targeted modifications of the ligand to enhance bioactivity.