Role of Nuclear Factor-κB in the Antiviral Action of Interferon and Interferon-regulated Gene Expression*

Interferons (IFNs) play critical roles in host defense by modulating the expression of various genes via tyrosine phosphorylation of STAT transcription factors. IFN-α/β activates another important transcription factor, nuclear factor-κB (NF-κB), but its role in IFN-mediated activity is poorly understood. Sensitivity to the antiviral and gene-inducing effects of IFN was examined in normal fibroblasts and in NF-κB knockout fibroblasts from p50- and p65-null mice. Antiviral assays demonstrated that NF-κB knockout fibroblasts were sensitized to the antiviral action of IFN. Moreover, analysis of IFN-stimulated gene expression by real-time PCR demonstrated selective effects of NF-κB on gene expression. Our results demonstrate that a subset of IFN-stimulated genes is regulated through an NF-κB-dependent pathway and that NF-κB may regulate the sensitivity of cells to IFN-mediated antiviral activity.

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