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J Immunol. 2011 Jan 15;186(2):1001-10. doi: 10.4049/jimmunol.1002240. Epub 2010 Dec 8.

Negative regulation of IRF7 activation by activating transcription factor 4 suggests a cross-regulation between the IFN responses and the cellular integrated stress responses.

Author information

  • 1Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.

Abstract

Cells react to viral infection by exhibiting IFN-based innate immune responses and integrated stress responses, but little is known about the interrelationships between the two. In this study, we report a linkage between these two host-protective cellular mechanisms. We found that IFN regulatory factor (IRF)7, the master regulator of type I IFN gene expression, interacts with activating transcription factor (ATF)4, a key component of the integrated stress responses whose translation is induced by viral infection and various stresses. We have demonstrated that IRF7 upregulates ATF4 activity and expression, whereas ATF4 in return inhibits IRF7 activation, suggesting a cross-regulation between the IFN response and the cellular integrated stress response that controls host innate immune defense against viral infection.

PMID:
21148039
[PubMed - indexed for MEDLINE]
PMCID:
PMC3057134
Free PMC Article

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