Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4-mediated IFN-beta induction
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概要
- 論文の詳細を見る
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.
- Oxford Univ Pressの論文
- 2008-09-01
著者
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MATSUMOTO MISAKO
Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine
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SEYA TSUKASA
Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine
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Ebihara Takashi
北海道大学 医学研究科免疫学
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Matsumoto Misako
北海道大学 医学研究科免疫学
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Matsumoto M
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Matsumoto Misako
Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases
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Seya Tsukasa
大阪府立成人病センター研究所 免疫学部門
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Seya Tsukasa
北海道大学 医学研究科免疫学
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Seya Tsukasa
Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases:probrain
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Ebihara Takashi
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Sasai Miwa
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Tsutsumi Hiroyuki
Department Of Pediatrics Sapporo Medical University School Of Medicine
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Seya Tsukasa
Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases
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松本 美佐子
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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FUNAMI Kenji
Department of Pharmaceutical Sciences, Hokkaido University
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Funami Kenji
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Ebihara Takashi
Department Of Mechanical Engineering Nagaoka University Of Technology
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Tsutsumi Hiroyuki
Department Of Pediatrics Sapporo Medical University
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AZUMA Masahiro
Department of Internal Medicine, Kaizuka City Hospital
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SHINGAI Masashi
Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine
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AYATA Minoru
Department of Virology, Osaka City University
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OGURA Hisashi
Department of Virology, Osaka City University
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Ayata Minoru
Department Of Virology Osaka City University
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Ogura Hisashi
Department Of Virology Osaka City University
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Seto Toshiyuki
Daparment Of Virology
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Tsutsumi Hiroyuki
Department of Pediatrics, Sapporo Medical University, School of Medicine
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