Interferon α/β

Type I interferons (IFNs) are key cytokines endowed with antiviral and immunomodulatory activities. The human type I IFN family consists of 13 subtypes of IFNα, a single IFNβ subtype, plus IFNε, IFNκ, and IFNϖ. Type I IFNs exert their biological activities via interaction with a heterodimeric receptor complex – a cell surface receptor composed of two subunits, namely IFNαR1 and IFNαR2. Ligand binding initiates a transcriptional program that leads to the expression of the IFN-regulated genes (IRGs) responsible for the multifaceted activity of type I IFNs. Optimal outcomes of these cytokines are achieved through regulation of the nature, strength, and duration of IFN production; IFN–receptor interaction; and specific signaling pathways that are modulated in a cell type–specific manner. When virus-infected cells are exposed to IFN, they develop what is known as an ‘antiviral state,’ regulated by the IRGs, in which the viral life cycle is blocked or impaired. However, viruses have developed an impressive array of tactics to circumvent IFN-mediated antiviral responses. Type I IFNs also induce a broad spectrum of cell activities, including cell proliferation and differentiation, angiogenesis, and immunomodulation, regulated by the release of mediators relevant for the innate and adaptive immune responses. Detailed knowledge about how these pathways are regulated will, in turn, further our understanding of the roles of IFN pathways in the pathogenesis of infectious and inflammatory diseases and cancer.