Global and Distinct Targets of IRF-5 and IRF-7 during Innate Response to Viral Infection

• Published in: The Journal of biological chemistry Vol. 279; no. 43; pp. 45194 - 45207
• Main Authors: Barnes, Betsy J, Richards, John, Mancl, Margo, Hanash, Sam, Beretta, Laura, Pitha, Paula M
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 22.10.2004
• Subjects: Blotting, Western; Carbon Tetrachloride - metabolism; Cell Line; Cell Line, Tumor; Chemokine CXCL11; Chemokines, CXC - metabolism; Dendritic Cells - metabolism; DNA - chemistry; DNA - metabolism; DNA, Complementary - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation; Humans; Inflammation; Interferon Regulatory Factor-7; Interferon Regulatory Factors; Interferon-beta - metabolism; Interferons - metabolism; Kinetics; Mitochondria - metabolism; Monocytes - metabolism; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Phosphorylation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Complementary - metabolism; RNA, Messenger - metabolism; Time Factors; Transcription Factors - chemistry; Transcription Factors - metabolism; Transcription, Genetic; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M400726200

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.