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Journal of Virology, March 2001, p. 3021-3027, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.3021-3027.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Downregulation of IRF-3 Levels by Ribozyme Modulates the Profile of IFNA Subtypes Expressed in Infected Human Cells

Wen-Shuz Yeow,1 Wei-Chun Au,1 William J. Lowther,1 and Paula M. Pitha1,2,*

Oncology Center1 and Department of Molecular Biology and Genetics,2 The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

Received 12 September 2000/Accepted 11 December 2000

As an early response to viral infection, cells express a number of cellular genes that play a role in innate immunity, including alpha/beta interferons (IFN). IFN-alpha /beta are encoded by a single IFNB gene and multiple, closely related IFNA genes. The induction of these IFN genes in infected cells occurs at the transcriptional level, and two transcription factors of the IRF family, IRF-3 and IRF-7, were shown to play a role in their activation. While the expression of IRF-3 alone was shown to be sufficient for induction of the IFNB gene, induction of all the IFNA subtypes in human cells required the presence of IRF-7. Since IRF-3 is expressed constitutively in all cells examined, the role of IRF-3 in the induction of IFNA genes has not been clarified. Using ribozyme targeted to IRF-3 mRNA, we found that the downregulation of IRF-3 levels in the infected cells inhibited not only the induction of IFNB gene but also the expression of IFNA genes. Furthermore, downmodulation of IRF-3 levels altered the expression profile of IFNA subtypes induced by viral infection. These studies suggest that the ratio between the relative levels of IRF-3 and IRF-7 is a critical determinant for the induction of the individual IFNA subtypes in infected cells.

* Corresponding author. Mailing address: The Johns Hopkins University, Bunting/Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231-1001. Phone: (410) 955-8871. Fax: (410) 955-0840. E-mail: parowe{at}jhmi.edu.

Journal of Virology, March 2001, p. 3021-3027, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.3021-3027.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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