Mechanisms of induction and action of interferons

Since the discovery that interferons responses constitute an efficient transition between innate and adaptive immunity to infectious microorganisms, the function and role of these cytokines are better understood. Interferons act on specific cell receptors, which activate well-defined transduction pathways to enhance the expression of hundreds of different Interferon-Stimulated Genes (ISGs) leading to the so-called antiviral state. Several of these genes including those encoding proteins (such as PKR, OAS, and ADAR1) depending on the presence of intracellular double stranded RNA for the activation of their enzymatic function, were studied in more detail. Considerable progress has been made recently in understanding how type I interferons expression is induced in response to virus infection. These imply several Toll-like Receptors (TLRs) and several newly described cytoplasmic protein sensors (RIG-I, MDA5, DAI) that detect the presence of viral nucleic acids and transduce intracellular signals leading to the activation of several members of the family of interferon regulatory factors (IRFs) required for the expression of type I interferons or directly some of the ISGs themselves. The discovery of these transduction pathways derives largely from the study of gene deficient cells and animals. The importance of these proteins is further attested by the discovery of several virally encoded antagonists that can interrupt specifically various steps of either the induction or the action of type I interferons.