非筋肉ミオシンIIAは,ヘルペスシンプレックスウイルス-1の機能的なエントリー受容体です
Jun Arii1, Hideo Goto, Tadahiro Suenaga
1Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Nature
|October 15, 2010
まとめ
非筋筋ミオシン重鎖IIA (NMHC-IIA) は,ヘルペス・シンプレックスウイルス-1 (HSV-1) のエントリー受容体として作用し,グリコプロテインB (gB) と相互作用します. この発見は,HSV-1感染症に対する抗ウイルス薬の開発のための新しい標的を明らかにします.
科学分野:
- ウイルス学 ウイルス学 ウイルス学
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- ヘルペス・シンプレックスウイルス-1 (HSV-1) は,粘膜皮膚疾患から致死性脳炎に至るまで,生涯にわたるヒト感染症を引き起こす.
- HSV-1の宿主細胞への侵入は,封筒型グリコタンパク質B (gB) とD (gD) の細胞受容体に依存する.
- HSV-1の広範囲の宿主とインビボ感染を媒介する特定のgB受容体は未だに特定されていない.
研究 の 目的:
- HSV-1グリコプロテインB (gB) の細胞受容体を特定する.
- HSV-1のエントリーにおける非筋肉ミオシン重鎖IIA (NMHC-IIA) の役割を調査する.
- 抗ウイルス療法における潜在的な標的として,NMHC-IIAを調査する.
主な方法:
- HSV-1耐性細胞におけるNMHC-IIAの過剰発現.
- NMHC-IIA.IIAに対する抗体を使用してHSV-1感染をブロックする.
- 許容性細胞におけるNMHC-IIAのノックダウン.
- HSV-1グリコプロテインによって媒介される細胞融合を評価する.
- NMHC-IIAの細胞表面表現のダイナミクスを調査する.
- 細胞培養におけるミオシン・ライトチェーンキナーゼ阻害剤とネズミのモデルを用いて.
主要な成果:
- 非筋肉性ミオシン重鎖IIA (NMHC-IIA) は,gB.と相互作用することにより,HSV-1のエントリー受容体として機能する.
- NMHC-IIAの過剰発現は,耐性細胞におけるHSV-1の感受性を有意に増加させた.
- NMHC-IIAとNMHC-IIAの抗体は,HSV-1感染を抑制した.
- NMHC-IIAの細胞表面発現は,HSV-1の侵入開始時に急速に誘発される.
- NM-IIA調節の阻害により,HSV-1感染はin vitroおよびin vivoで減少しました.
結論:
- NMHC-IIAは,gBと相互作用する機能的なHSV-1エントリー受容体として特定されています.
- NMHC-IIAは,広範囲のHSV-1感染性をインビトロおよびインビボで媒介する.
- NM-IIAの調節は,HSV-1感染において極めて重要であり,新たな抗ウイルス薬標的を提示する.
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