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.