Functional characterization of murine interferon regulatory factor 5 (IRF-5) and its role in the innate antiviral response
Authors
Paun, AndreaReinert, Jorgen T.
Jiang, Zhaozhao
Medin, Carey L.
Balkhi, Mumtaz Yaseen
Fitzgerald, Katherine A.
Pitha, Paula M.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2008-03-12Keywords
Alternative SplicingAmino 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
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2008 May 23;283(21):14295-308. Epub 2008 Mar 10. Link to article on publisher's siteDOI
10.1074/jbc.M800501200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35237PubMed ID
18332133Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M800501200