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Mechanism of up-regulation of human Toll-like receptor 3 secondary to infection of measles virus-attenuated strains.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2003 Nov 07; Vol. 311 (1), pp. 39-48. - Publication Year :
- 2003
-
Abstract
- PolyI:C, a synthetic double-stranded (ds)RNA, and viruses act on cells to induce IFN-beta which is a key molecule for anti-viral response. Although dsRNA is a virus-specific signature and a ligand for human Toll-like receptor 3 (TLR3), largely uncharacterized multiple pathways associate virus-mediated IFN-beta induction. Here, we demonstrated that laboratory-adapted but not wild-type strains of measles virus (MV) up-regulated TLR3 expression both in dendritic cells and epithelial cell line A549. The kinetics experiments with the laboratory MV strain revealed that TLR3 was induced late compared to IFN-beta and required new protein synthesis. Furthermore, neutralizing antibodies against IFN-beta or IFNAR (Interferon-alpha/beta receptor) suppressed MV-induced TLR3 induction, indicating that type I IFN, IFN-alpha/beta, is critical for MV-mediated TLR3 induction. Yet, a recently identified virus-inducible IFN, the IFN-lambda, did not contribute to TLR3 expression. A virus-responsive element that up-regulates TLR3 was identified in the TLR3-promoter region by reporter gene experiments. The ISRE, a recently reported site for IFN-beta induction, but not STAT binding site, located around -30bp of TLR3 promoter responded to MV to induce TLR3 expression. This further indicates the importance of type I IFN for TLR3 up-regulation in the case of viral infection. In HeLa and MRC5 cells, augmented production of IFN-beta was observed in response to dsRNA when TLR3 had been induced beforehand. Thus, the MV-induced expression of TLR3 may reflect amplified IFN production that plays a part in host defense to viral infection.
- Subjects :
- Cell Line
Fibroblasts immunology
Fibroblasts metabolism
Fibroblasts virology
Humans
Measles immunology
Measles virus classification
Measles virus immunology
Membrane Glycoproteins classification
Membrane Glycoproteins immunology
Receptors, Cell Surface classification
Receptors, Cell Surface immunology
Respiratory Mucosa immunology
Respiratory Mucosa metabolism
Respiratory Mucosa virology
Toll-Like Receptor 3
Toll-Like Receptors
Vaccines, Attenuated
Interferon-beta immunology
Interferon-beta metabolism
Measles metabolism
Measles virus pathogenicity
Membrane Glycoproteins metabolism
Receptors, Cell Surface metabolism
Up-Regulation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 311
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 14575692
- Full Text :
- https://doi.org/10.1016/j.bbrc.2003.09.159