Interferon at 50: new molecules, new potential, new (and old) questions.
Type I interferons (IFNs) are a family of cytokines defined by their antiviral activity but with a broad spectrum of biological activities, including antiproliferative, antitumor, and immunomodulatory effects. Mirroring these activities are diverse therapeutic applications to viral infections, antitumor therapy, and multiple sclerosis. The type I IFNs all signal through a common heterodimeric receptor. The existence of such a large family of cytokines (17 human IFNs) activating a common receptor is unusual. Moreover, the IFNs vary in their relative potency in different assays and are not functionally equivalent. How this functional variation is mediated through a common receptor has not been understood. Reports have now highlighted the interaction of IFNs with the low-affinity receptor subunit IFNAR-1 as a surprising key to their differential activity, particularly regarding antiproliferative and antitumor activities. Two groups have used contrasting approaches to produce variant IFN-alpha proteins with novel activity profiles. These advances portend enhanced therapeutic possibilities based on the better understanding of IFN-receptor interactions, while raising interesting mechanistic questions.
Langer
Jerome A
JA
Department of Molecular Genetics, Microbiology, and Immunology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA. langer@umdnj.edu
D006801:Humans; D007372:Interferons / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D011485:Protein Binding; D017471:Receptors, Interferon / Q000378:metabolism
D017471:Receptors, Interferon; D007372:Interferons