Functional characterization of interferon regulatory factor 3a (IRF-3a), an alternative splice isoform of IRF-3

Virus infection of numerous cell types results in the transcriptional induc tion of a subset of virus- and interferon (IFN)-stimulated genes. The beta IFN (IFN-beta) gene is one of these rapidly induced genes; it serves as a f undamental component of the cellular defense response in eliciting potent a ntiviral, immunomodulatory, and antiproliferative effects. One of the trans cription factors involved in the stringent regulation of IFN-beta productio n following virus infection is interferon regulatory factor (IRF) 3 (IRF3). We have characterized an alternatively spliced isoform of IRF3 that we hav e called IRF-3a. IRF-3a can selectively and potently inhibit virus-induced activation of the IFN-beta promoter. IRF-3a lacks half of the DNA binding d omain found in IRF-3 and is unable to bind to the classical IRF binding ele ments, IFN-stimulated response elements. These studies suggest that IRF-3a may act as a modulator of IRF3.