TYPE-I INTERFERONS - EXPRESSION AND SIGNALIZATION

Type I interferon (IFN-A and IFN-B) genes encode a large family of mul tifunctional secreted proteins involved in antiviral defence, cell gro wth regulation and immune activation. These cytokines, as a consequenc e of their biological activities, have been established as effective t herapeutic molecules for malignant and viral diseases. Virus infection is the main inducer leading to transient expression of type I IFN (A and B) and the antiviral response appears to proceed through a two-ste p pathway requiring, first, induction of type I IFN gene expression an d, second, transcriptional activation by the synthesized IFN proteins, binding to their specific cell surface receptors, of a large number o f genes. The proteins they encode are responsible, in part, for the pl eiotropic multiple biological activities of the IFN. In this two-step pathway, the virus-induced IFN genes and the IFN-stimulated gene (ISG) expression seem to share common factors. Even if IFN-A genes are stru cturally related and very often coordinately induced in virus-infected cells, differences in the expression of the individual IFN-A messenge r RNAs of the multigenic IFN-A gene family are observed in human as we ll as in murine cells, reflecting, in a particular cell type, the tran scriptional activity of the corresponding promoter regions. Important studies on interferon regulatory factors and ISG factors have been mad e in the last decade. However, some factors involved in IFN-A gene reg ulation remain to be identified. Our goal has been to review the facto rs involved in the control of the type I IFN gene expression to unders tand the mechanisms of induction and repression of their transcription and to explain the properties of these cytokines through their signal transduction pathway.