Functional Characterization of Interferon Regulatory Factor 3a (IRF-3a), an Alternative Splice Isoform of IRF-3

Abstract

Virus infection of numerous cell types results in the transcriptional induction of a subset of virus- and interferon (IFN)-stimulated genes. The beta IFN (IFN-β) gene is one of these rapidly induced genes; it serves as a fundamental component of the cellular defense response in eliciting potent antiviral, immunomodulatory, and antiproliferative effects. One of the transcription factors involved in the stringent regulation of IFN-β production following virus infection is interferon regulatory factor (IRF) 3 (IRF-3). We have characterized an alternatively spliced isoform of IRF-3 that we have called IRF-3a. IRF-3a can selectively and potently inhibit virus-induced activation of the IFN-β promoter. IRF-3a lacks half of the DNA binding domain found in IRF-3 and is unable to bind to the classical IRF binding elements, IFN-stimulated response elements. These studies suggest that IRF-3a may act as a modulator of IRF-3.

ACKNOWLEDGMENTS

We thank Charles Ro for expert technical assistance. We thank Maren Trost for helpful discussions and critical review of the manuscript.

L.V.R. was supported by fellowship grant 5 F32 AI09167-02 from the National Institute of Allergy and Infectious Diseases and a grant from Aid for Cancer Research. A.Y.K. is a Howard Hughes Medical Institute predoctoral fellow. This research was supported by National Institute of Health grant PO1 AI 42257 to P.M.H.

Alla Y. Karpova and Lucienne V. Ronco contributed equally to the work described in this article.