ノロウイルスに対するタンパク質細胞受容体の発見
Robert C Orchard1, Craig B Wilen1, John G Doench2
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science (New York, N.Y.)
|August 20, 2016
まとめ
ノロウイルス (NoV) は胃腸炎の主な原因です. 研究者らは,CD300lfがネズミのNoV (MNoV) 感染に不可欠なタンパク質受容体として作用し,宿主範囲を決定することを発見した.
科学分野:
- ウイルス学
- 免疫学
- 構造生物学
背景:
- ノロウイルス (NoVs) は,胃腸炎の重要な世界的な原因です.
- NoV感染を可能にする宿主要因を理解することは,制御戦略の開発に不可欠です.
研究 の 目的:
- マウリン・ノロウイルス (MNoV) 感染に不可欠な宿主分子を特定する.
- 特定された宿主因子のMNoV結合,複製,種のトロピズムにおける役割を明らかにする.
主な方法:
- MNoVによる細胞死に関与する宿主因子を特定するための細胞ベースの測定法.
- マウスにおける特定宿主因子 (Cd300lf) の遺伝子ノックアウト
- MNoVの複製を評価するために,ヒト細胞におけるヒトCD300lfの発現.
- CD300lfエクトドメインの構造を決定する結晶学.
主要な成果:
- CD300lfは,MNoVの結合と細胞系および原細胞における複製に不可欠なタンパク質受容体として特定されました.
- Cd300lf ノックアウトマウスはMNoV感染に耐性を示した.
- ヒトのCD300lfの発現により,ヒトの細胞でMNoVの複製が可能になり,種の障壁を突破しました.
- 構造分析により,MNoV感染に重大なCD300lfの結合裂けが明らかになった.
結論:
- CD300lfは,主要なタンパク質受容体として作用するMNoV種のトロピズムを決定する重要な要素です.
- NOV複製のための細胞機構はマウスとヒトの間に保存され,受容体は主要な特異性因子である.
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