Global and Distinct Targets of IRF-5 and IRF-7 during Innate Response to Viral Infection
The interferon regulatory factors (IRF) are transcriptional mediators of cellular response to viral invasion that play a critical role in the innate antiviral defense. Two of these factors, IRF-5 and IRF-7, play a critical role in the induction of interferon ( IFNA ) genes in infected cells; they ar...
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Published in | The Journal of biological chemistry Vol. 279; no. 43; pp. 45194 - 45207 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
22.10.2004
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Subjects | |
Online Access | Get full text |
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Summary: | The interferon regulatory factors (IRF) are transcriptional mediators of cellular response to viral invasion that play a critical
role in the innate antiviral defense. Two of these factors, IRF-5 and IRF-7, play a critical role in the induction of interferon
( IFNA ) genes in infected cells; they are expressed constitutively in monocytes, B cells, and precursors of dendritic cells (pDC2)
that are high producers of interferon α, and their expression can be further stimulated by type I interferon. The goal of
the present study was to identify and analyze expression of cellular genes that are modulated by IRF-5 and IRF-7 during the
innate response to viral infection. The transcription profiles of infected BJAB cells overexpressing IRF-5 or IRF-7 were determined
by using oligonucleotide arrays with probe sets representing about 6800 human genes. This analysis shows that IRF-5 and IRF-7
activate a broad profile of heterologous genes encoding not only antiviral, inflammatory, and pro-apoptotic proteins but also
proteins of other functional categories. The number of IRF-5- and IRF-7 -modulated genes was significantly higher in infected than in uninfected cells, and the transcription signature was predominantly
positive. Although IRF-5 and IRF-7 stimulated a large number of common genes, a distinct functional profile was associated
with each of these IRFs. The noted difference was a broad antiviral and early inflammatory transcriptional profile in infected
BJAB/IRF-5 cells, whereas the IRF-7-induced transcripts were enriched for the group of mitochondrial genes and genes affecting
the DNA structure. Taken together, these data indicate that IRF-5 and IRF-7 act primarily as transcriptional activators and
that IRF-5-and IRF-7-induced innate antiviral response results in a broad alteration of the transcriptional profile of cellular
genes. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M400726200 |