Ubiquitously expressed interferon regulatory factor 3 (IRF-3)
is directly activated after virus infection and functions as a
key activator of the immediate-early alpha/beta interferon (IFN)
genes, as well as the RANTES chemokine gene. In the present study,
a tetracycline-inducible expression system expressing a constitutively
active form of IRF-3 (IRF-3 5D) was combined with DNA microarray
analysis to identify target genes regulated by IRF-3. Changes
in mRNA expression profiles of 8,556 genes were monitored after
Tet-inducible expression of IRF-3 5D. Among the genes upregulated
by IRF-3 were transcripts for several known IFN-stimulated genes
(ISGs). Subsequent analysis revealed that IRF-3 directly induced
the expression of ISG56 in an IFN-independent manner through the
IFN-stimulated responsive elements (ISREs) of the ISG56 promoter.
These results demonstrate that, in addition to its role in the
formation of a functional immediate-early IFN-beta enhanceosome,
IRF-3 is able to discriminate among ISRE-containing genes involved
in the establishment of the antiviral state as a direct response
to virus infection.