ロタウイルスはADPシグナル伝達を通じて細胞間カルシウム波を誘発する
Alexandra L Chang-Graham1,2, Jacob L Perry1,2, Melinda A Engevik3,4
1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Science (New York, N.Y.)
|November 20, 2020
まとめ
ロタウイルス感染症は,細胞外アデノシン5'- 二酸化物 (ADP) とP2Y1受容体を通して細胞間カルシウム波 (ICW) を引き起こす. このシグナル伝達経路を遮断すると,ネズミのロタウイルス複製と下痢の重症度が低下します.
科学分野:
- 胃腸内科
- ウイルス学
- 細胞生物学
背景:
- ロタウイルス感染症は,腸内ホメオスタシスを乱すことで,重度の下痢疾患を引き起こす.
- ロタウイルスに起因する腸の調節障害の正確なメカニズムは完全に理解されていません.
研究 の 目的:
- ロタウイルスが腸内ホメオスタシスを破壊するメカニズムを解明する.
- ロタウイルス病原性における細胞間カルシウム波 (ICW) の役割を調査する.
主な方法:
- ロタウイルスに感染した細胞系とヒト腸内小胞体のICWの観察
- 信号分子として細胞外アデノシン5"二酸化物 (ADP) の識別.
- P2Y1受容体アンタゴニストとCRISPR- Cas9遺伝子編集を活用して,純エネルギー信号をブロックした.
- 新生児マウスのロタウイルス複製,宿主反応,および下痢の重度に対するADP信号の阻害の影響を評価した.
主要な成果:
- ロタウイルス感染は,細胞外ADPがP2Y1純素受容体を活性化することで,ICWを誘発した.
- P2Y1シグナル伝達の阻害はICWを阻害し,ロタウイルス複製を減少させ,ロタウイルス誘発のセロトニン放出と流体分泌を減少させた.
- 新生児マウスモデルでは,ADP- P2Y1経路を遮断することで,下痢の重症度が著しく低下しました.
結論:
- ロタウイルスはパラクリン・ピューリナージックシグナリング,特にP2Y1受容体に作用するADPを利用してICWを生成します.
- これらのICWは宿主細胞の異常を拡大し,胃腸の生理を変化させ,ロタウイルスによる下痢に寄与する.
- この純粋性信号伝達経路をターゲットにすることは,ロタウイルス感染症の管理のための潜在的な治療戦略です.
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