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Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4-mediated IFN-beta induction

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Title: Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4-mediated IFN-beta induction
Other Titles: Blocking TLR-TICAM-1 pathway by RSV sG
Authors: Shingai, Masashi Browse this author
Azuma, Masahiro Browse this author
Ebihara, Takashi Browse this author
Sasai, Miwa Browse this author
Funami, Kenji Browse this author
Ayata, Minoru Browse this author
Ogura, Hisashi Browse this author
Tsutsumi, Hiroyuki Browse this author
Matsumoto, Misako Browse this author →KAKEN DB
Seya, Tsukasa Browse this author →KAKEN DB
Keywords: Toll-like receptor
TICAM-1 (TRIF)
respiratory syncytial virus
type I interferons
dendritic cells
Issue Date: Sep-2008
Publisher: Oxford Univ Press
Journal Title: International Immunology
Volume: 20
Issue: 9
Start Page: 1169
End Page: 1180
Publisher DOI: 10.1093/intimm/dxn074
PMID: 18611945
Abstract: Monocyte-derived dendritic cells (mDCs) recognize viral RNA extrinsically by TLR3 on the membrane and intrinsically RIG-I/MDA5 in the cytoplasm to induce type I interferons (IFNs) and mDC maturation. When mDCs were treated with live or UV-irradiated respiratory syncytial virus (RSV), early (~4 h) induction of IFN-β detected in other virus infections was barely observed. Live RSV subsequently replicated to activate the cytoplasmic IFN-inducing pathway leading to robust type I IFN induction. We found that RSV initial attachment to cells blocked polyI:C-mediated IFN-β induction, and this early IFN-β-modulating event was abrogated by Abs against envelope proteins of RSV, demonstrating the presence of a IFN-regulatory mode by early RSV attachment to host cells. By IFN-stimulated response element (ISRE) reporter analysis in HEK293 cells, polyI:C- or LPS-mediated ISRE activation was dose-dependently inhibited by live and inactive RSV to a similar extent. Of the RSV envelope proteins, simultaneously-expressed or exogenously-added RSV G or soluble G (sG) proteins inhibited TLR3/4-mediated ISRE activation in HEK293 cells. sG proteins expressed in cells did not affect the RIG-I/MDA5 pathway but inhibited the TLR adaptor TRIF/TICAM-1 pathway for ISRE activation. Finally, extrinsically-added sG protein suppressed the production of IFN-β in mDCs. Although the molecular mechanism of this extrinsic functional mode of the RSV G protein remains undetermined, G proteins may neutralize the F protein function that promotes IFN-mediated mDC modulation via TLR4 and may cause insufficient raising cell-mediated immunity against RSV.
Rights: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in "International Immunology" following peer review. The definitive publisher-authenticated version "International Immunology 2008 20(9):1169-1180" is available online at: http://dx.doi.org/10.1093/intimm/dxn074
Type: article (author version)
URI: http://hdl.handle.net/2115/39130
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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