HIV-1 プロウイルス単体の転写,統合,および配列の並列分析
Kevin B Einkauf1, Matthew R Osborn1, Ce Gao2
1Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Cell
|January 13, 2022
まとめ
持続的なHIV-1感染は 静かなウイルスだけでなく 転写的に活性なプロウイルスを含みます これらの活性ウイルス貯蔵体は宿主選択の圧力下で進化し,抗レトロウイルス療法 (ART) 中のウイルス潜伏期に関する伝統的な見解に異議を唱える.
科学分野:
- ウイルス学
- ゲノミクス
- エピジェネティクス
背景:
- 抗レトロウイルス治療 (ART) 中のヒト免疫不全ウイルス1型 (HIV-1) に感染した細胞は,しばしば転写的に静止していると考えられ,ウイルスの潜伏を示します.
- しかし,証拠は,HIV-1の潜伏の確立された概念に疑問を投げかけ,活発なウイルスの遺伝子発現がいくつかの持続的な細胞で起こる可能性があることを示唆しています.
研究 の 目的:
- 複写的に活発で静かなHIV-1プロウイルスに関する包括的なゲノムと表遺伝子図を作成する.
- 抑制性ARTを投与された個体におけるこれらの前ウイルス状態の縦方向の進化を分析する.
- プロウイルスの転写活動,宿主染色体の特徴,選択圧力の関係を調べる.
主な方法:
- HIV-1 プロウイルスの転写活動と染色体の位置をプロファイルするための新しい測定法の開発と適用.
- ゲノム全体のエピジェネティック基準データを統合して,プロウイルス活性とクロマチンの状態を相関させる.
- 抑制性ARTを投与された患者におけるプロウィルス進化の縦断分析
主要な成果:
- プロバイラル転写活性は,統合部位付近および3Dゲノム接触部位のエピジェネティッククロマチン特性の活性化に関連しています.
- トランスクリプションが活発なプロウイルスは,通常,長期のARTで選択されます.
- 感染した細胞の大型クローンは 増殖能力が高く ネガティブ・セレクションを克服し 活発なプロウイルスを維持できます
結論:
- この研究は,トランスクリプションが活発で,静かなHIV-1プロウイルスのダイナミックな風景を明らかにしています.
- プロバイラル転写活動は宿主の表遺伝子環境と選択圧力によって影響を受けます.
- 活発なプロウイルスは静的ではなく,宿主因子と細胞増殖ダイナミクスの影響下で進化する.
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