IGF1Rは呼吸器シンチチアルウイルスのエントリー受容体である

Cameron D Griffiths^1,2, Leanne M Bilawchuk^1,2, John E McDonough³

¹Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.

Nature

|June 5, 2020

まとめ

呼吸器同胞ウイルス (RSV) は,核素を細胞侵入の共同受容体として使用する. タンパク質キナーゼCゼタ (PKCζ) を阻害することで,ヌクレオリン輸送を阻害し,RSVの複製と病理を減少させます.

科学分野:

ウイルス学
細胞生物学
免疫学

背景:

肺炎は世界の主要な死因であり,呼吸器同胞性ウイルス (RSV) は健康に重大な負担を及ぼし,治療の選択肢は限られている.
RSVは毛細管の上皮細胞に感染しますが,ウイルスの侵入と受容体の相互作用の正確なメカニズムは不明です.
核素はRSVや他の病原体へのエントリー共受容体として作用し,細胞への侵入を促進します.

研究の目的:

RSVが宿主細胞に侵入するメカニズムを解明する.
RSV感染における特定の細胞信号伝達経路とコレセプターの役割を特定する.
RSVの侵入メカニズムを理解することによって,潜在的な治療標的を探求する.

主な方法:

RSV- Fグリコタンパク質とインスリン類似成長因子-1受容体の相互作用を調べてRSVへの侵入を調査した.
タンパク質キナーゼCゼタ (PKCζ) のシグナル伝達が核素を細胞膜に誘導する役割を研究した.
PKCζ活性化抑制の影響を評価するために,呼吸道器官培養物とRSV感染マウスモデルを使用した.

主要な成果:

インスリン類似成長因子1受容体へのRSV- Fの結合がPKCζの活性化を誘発することを示した.
活性化されたPKCζシグナリングは,核から核素をプラズマ膜に誘導し,そこでRSV粒子と結合する.
PKCζの活性化を阻害することで,RSV粒子へのニュクレオリン輸送を防止し,ウイルス複製と病理性を in vivoで減少させました.

結論:

RSVの侵入は,受容体の関与が細胞表面のウイルス粒子へのコレセプター徴募につながるシグナリングカスケードを含みます.
PKCζとヌクレオリンが関与する特定された経路は,ウイルスの侵入の新しいメカニズムを表しています.
この経路をターゲットにすることで,RSV感染に対する新しい治療戦略の開発が可能になります.

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