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Mechanism of up-regulation of human Toll-like receptor 3 secondary to infection of measles virus-attenuated strains

by Masako Tanabe, Mitsue Kurita-Taniguchi, Kaoru Takeuchi, Makoto Takeda, Minoru Ayata, Hisashi Ogura, Misako Matsumoto, Tsukasa Seya
Biochemical and Biophysical Research Communications ()

Abstract

PolyI:C, a synthetic double-stranded (ds)RNA, and viruses act on cells to induce IFN-?? 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-?? 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-?? and required new protein synthesis. Furthermore, neutralizing antibodies against IFN-?? or IFNAR (Interferon-??/?? receptor) suppressed MV-induced TLR3 induction, indicating that type I IFN, IFN-??/??, is critical for MV-mediated TLR3 induction. Yet, a recently identified virus-inducible IFN, the IFN-??, 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-?? 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-?? 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. ?? 2003 Elsevier Inc. All rights reserved.

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