Abstract
Activation of the transcription factor interferon regulatory factor-3 (IRF-3) is an essential event in the innate immune response to viral infection. To understand the contribution of IRF-3 to host defense, we used a systems biology approach to analyze global gene expression dependent on IRF-3. Comparison of expression profiles in cells from IRF-3 knockout animals or wild-type siblings following viral infection revealed three sets of induced genes, those that are strictly dependent on IRF-3, augmented with IRF-3, or not responsive to IRF-3. Products of identified IRF-3 target genes are involved in innate or acquired immunity, or in the regulation of cell cycle, apoptosis and proliferation. These results reveal the global effects of one transcription factor in the immune response and provide information to evaluate the integrated response to viral infection.
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Acknowledgements
We thank all the members of the laboratory for support and discussions. We gratefully acknowledge Dr Tadasugu Taniguchi (University of Tokyo) for providing us with cells from WT and IRF-3 KO animals. We also thank John Schwedes at the Affymetrix core facility for his role in processing and analyzing the microarrays, and Michelle Massoth for help with Genesifter Software (www.genesifter.net). We are grateful to Dr Herb Lewis and Robert Andersen for writing a Visual Basic code used for secondary comparisons. Human IFN-αA was a kind gift of Hoffman-LaRoche, NJ, USA). These studies were supported by grants from NIH (R21AI067885 and PO1AI0555621).
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Andersen, J., VanScoy, S., Cheng, TF. et al. IRF-3-dependent and augmented target genes during viral infection. Genes Immun 9, 168–175 (2008). https://doi.org/10.1038/sj.gene.6364449
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DOI: https://doi.org/10.1038/sj.gene.6364449
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