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Journal of Virology, March 2001, p. 3021-3027, Vol. 75, No. 6
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-
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
/
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.
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