論文

2008年9月

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

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

20
9
開始ページ
1169
終了ページ
1180
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/intimm/dxn074
出版者・発行元
OXFORD UNIV PRESS

Monocyte-derived dendritic cells (mDCs) recognize viral RNA extrinsically by Toll-like receptor (TLR)3 on the membrane and intrinsically retinoic acid-inducible on the membrane and intrinsically retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm to induce type I IFNs and mDC maturation. When mDCs were treated with live or UV-irradiated respiratory syncytial virus (RSV), early (similar to 4h) induction of IFN-beta usually occurs 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-beta induction, and this early IFN-beta-modulating event was abrogated by antibodies 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) receptor analysis in HEK293 cells, polyI:C- 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 TLR/4-mediated ISRE activation in HEK293 cells. sG proteins expressed in cells did not affect the RIG-1/MDA5 pathway but inhibited the TLR adaptor TRIF/TICAM-1 pathway for ISRE activation. Finally, extrinsically added sG protein suppressed the production of IFN-beta in mDCs. Although the molecular mechanism of this extrinsic functional mode of the RSV G glycoprotein (G protein) remains undetermined, G proteins may neutralize the fusion glycoprotein function that promotes IFN-mediated mDC modulation via TCR4 and may cause insufficient raising cell-mediated immunity against RSV.

Web of Science ® 被引用回数 : 57

リンク情報
DOI
https://doi.org/10.1093/intimm/dxn074
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000259301300007&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/intimm/dxn074
  • ISSN : 0953-8178
  • Web of Science ID : WOS:000259301300007

エクスポート
BibTeX RIS