Title
Functional characterization of murine interferon regulatory factor 5 (IRF-5) and its role in the innate antiviral response
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2008-03-12
Document Type
Article
Subjects
Alternative Splicing; Amino Acid Sequence; Animals; Cell Line; Conserved Sequence; Cytokines; Dimerization; Humans; Interferon Regulatory Factors; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Newcastle Disease; Promoter Regions, Genetic; Protein Binding; Sequence Alignment; Toll-Like Receptors; Transcription, Genetic
Disciplines
Immunology and Infectious Disease
Abstract
Although the role of human IRF-5 in antiviral and inflammatory responses in vitro has been well characterized, much remains to be elucidated about murine IRF-5. Murine IRF-5, unlike the heavily spliced human gene, is primarily expressed as a full-length transcript, with only a single splice variant that was detected in very low levels in the bone marrow of C57BL/6J mice. This bone marrow variant contains a 288-nucleotide deletion from exons 4-6 and exhibits impaired transcriptional activity. The murine IRF-5 can be activated by both TBK1 and MyD88 to form homodimers and bind to and activate transcription of type I interferon and inflammatory cytokine genes. The importance of IRF-5 in the antiviral and inflammatory response in vivo is highlighted by marked reductions in serum levels of type I interferon and tumor necrosis factor alpha (TNFalpha) in Newcastle disease virus-infected Irf5(-)(/)(-) mice. IRF-5 is critical for TLR3-, TLR4-, and TLR9-dependent induction of TNFalpha in CD11c(+) dendritic cells. In contrast, TLR9, but not TLR3/4-mediated induction of type I IFN transcription, is dependent on IRF-5 in these cells. In addition, IRF-5 regulates TNFalpha but not type I interferon gene transcription in Newcastle disease virus-infected peritoneal macrophages. Altogether, these data reveal the cell type-specific importance of IRF-5 in MyD88-mediated antiviral pathways and the widespread role of IRF-5 in the regulation of inflammatory cytokines.
DOI of Published Version
10.1074/jbc.M800501200
Source
J Biol Chem. 2008 May 23;283(21):14295-308. Epub 2008 Mar 10. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
18332133
Repository Citation
Paun A, Reinert JT, Jiang Z, Medin CL, Balkhi M, Fitzgerald KA, Pitha PM. (2008). Functional characterization of murine interferon regulatory factor 5 (IRF-5) and its role in the innate antiviral response. Infectious Diseases and Immunology Publications. https://doi.org/10.1074/jbc.M800501200. Retrieved from https://escholarship.umassmed.edu/infdis_pp/71