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

Shingai, Masashi; Azuma, Masahiro; Ebihara, Takashi; Sasai, Miwa; Funami, Kenji; Ayata, Minoru; Ogura, Hisashi; Tsutsumi, Hiroyuki; Matsumoto, Misako; Seya, Tsukasa

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

Shingai, Masashi; Azuma, Masahiro; Ebihara, Takashi et al.

International Immunology, 2008, 20(9), 1169-1180

Permalink : https://hdl.handle.net/2115/39130

このアイテムのアクセス数:1,589件（2026-10-12 07:26 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
RSV_3r	pdf	1.24 MB	1,483

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/39130
タイトル	Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4-mediated IFN-beta induction
その他のタイトル	Blocking TLR-TICAM-1 pathway by RSV sG
著者	Shingai, Masashi ; Azuma, Masahiro ; Ebihara, Takashi ; Sasai, Miwa ; Funami, Kenji ; Ayata, Minoru ; Ogura, Hisashi ; Tsutsumi, Hiroyuki ; Matsumoto, Misako ; Seya, Tsukasa
著者名 Shingai, Masashi
著者名 Azuma, Masahiro
著者名 Ebihara, Takashi
著者名 Sasai, Miwa
著者名 Funami, Kenji
著者名 Ayata, Minoru
著者名 Ogura, Hisashi
著者名 Tsutsumi, Hiroyuki
e-Rad_Researcher 30332456 著者名 Matsumoto, Misako
e-Rad_Researcher 10301805 著者名 Seya, Tsukasa
言語	英語
キーワード	Toll-like receptor
	TICAM-1 (TRIF)
	respiratory syncytial virus
	type I interferons
	dendritic cells
発行日	2008-09
出版者	Oxford Univ Press
収録物名	International Immunology
巻(号)	20(9)
ページ	1169-1180
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	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
PISSN	0953-8178
EISSN	1460-2377
NCID	AA10730708
関連情報	PMID 18611945
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1093/intimm/dxn074