コトランスレーションによるプロリル水酸化は,フラビウイルスバイオゲネシスに不可欠である
Ranen Aviner1,2, Kathy H Li3, Judith Frydman4
1Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Nature
|August 19, 2021
まとめ
ポリオ,デング熱,ジカのようなウイルスは 宿主細胞の仕組みを ポリソームと呼ばれる タンパク質を作る複合体を 変えて乗っ取ります これらのウイルスポリソームをターゲットにすることで 新しい抗ウイルス戦略が生まれます
科学分野:
- ウイルス学
- 分子生物学
- 生物化学
背景:
- ウイルスの病原体は 世界的に公衆衛生に重大な脅威をもたらしています
- ウイルスと宿主の相互作用を理解することは,抗ウイルス療法の開発に不可欠です.
- ホストの生物合成経路は ウイルスの複製に不可欠です
研究 の 目的:
- エントロウイルスとフラビウイルスが宿主ポリソームを再構成する方法を調査する.
- ウイルスがタンパク質合成のために利用する宿主機構を特定する.
- 抗ウイルス戦略として ウイルスポリソームを標的にする
主な方法:
- ポリソームのプロテオミック分析
- 機能的なゲノミクスです
- 薬学的な介入
- ウイルスのタンパク質の変異の分析
主要な成果:
- ウイルス感染 (ポリオ,デング熱,ジカ) は,リボソームのステキオメトリーを変えることなく,ポリソームの組成を変えます.
- ウイルスは共通の翻訳因子を排除し 特定の宿主機構を勧誘します
- ジカウイルスとデング熱ウイルスは コラーゲンプロリン水酸化により ウイルスのポリタンパク質を改変します
- プロリン水酸化抑制はウイルスのポリタンパク質の折り畳みを阻害し,ウイルス産生を減少させます.
結論:
- ウイルスのポリソームの再構築は,ウイルス-宿主インターフェイスでモジュール化されたプロセスです.
- 特殊なウイルスポリソームをターゲットにすることで,有望な抗ウイルス介入方法が提供されます.
- プロリン水酸化はデング熱やジカウイルスが利用する 主要な宿主因である.
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