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Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes.

http://www.ncbi.nlm.nih.gov/pubmed/11303025

Interferon regulatory factor (IRF) genes encode DNA-binding proteins that are involved in the innate immune response to infection. Two of these proteins, IRF-3 and IRF-7, serve as direct transducers of virus-mediated signaling and play critical roles in the induction of type I interferon genes. We have now shown that another factor, IRF-5, participates in the induction of interferon A (IFNA) and IFNB genes and can replace the requirement for IRF-7 in the induction of IFNA genes. We demonstrate that, despite the functional similarity, IRF-5 possesses unique characteristics and does not have a redundant role. Thus, 1) activation of IRF-5 by phosphorylation is virus-specific, and its in vivo association with the IFNA promoter can be detected only in cells infected with NDV, not Sendai virus, while both viruses activate IRF-3 and IRF-7, and 2) NDV infection of IRF-5-overexpressing cells preferentially induced the IFNA8 subtype, while IFNA1 was primarily induced in IRF-7 expressing cells. These data indicate that multiple signaling pathways induced by infection may be differentially recognized by members of the IRF family and modulate transcription of individual IFNA genes in a virus and cell type-specific manner.

Pubmed ID: 11303025 RIS Download

Mesh terms: B-Lymphocytes | Base Sequence | Cell Line | Cell Nucleus | DNA-Binding Proteins | Dendritic Cells | HeLa Cells | Humans | Interferon Regulatory Factor-3 | Interferon Regulatory Factors | Interferon-alpha | Interferon-beta | Lymphoid Tissue | Molecular Sequence Data | Newcastle disease virus | Promoter Regions, Genetic | Protein Structure, Tertiary | RNA, Messenger | Respirovirus | Response Elements | Species Specificity | Trans-Activators | Transcription Factors | Transcriptional Activation