Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
Peer-reviewed Journal Articles, etc >
Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4-mediated IFN-beta induction
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
|