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Molecular and Cellular Biology, July 2001, p. 4169-4176, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4169-4176.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Alla Y. Karpova,¹ Lucienne V. Ronco,^1, and Peter M. Howley^1,*

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115¹

Received 30 November 2000/Returned for modification 22 January 2001/Accepted 30 March 2001

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-) 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- 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- 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.

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^* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, Boston, MA 02115. Phone: (617) 432-2884. Fax: (617) 432-2882. E-mail: peter_howley{at}hms.harvard.edu.

Present address: Pfizer Inc., Discovery Technology Center, Cambridge, MA 02139.

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Molecular and Cellular Biology, July 2001, p. 4169-4176, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4169-4176.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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