CGダイヌクレオチド抑制は,非自己RNAを標的とした抗ウイルス防御を可能にします

Matthew A Takata¹, Daniel Gonçalves-Carneiro¹, Trinity M Zang^1,2

¹Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA.

Nature

|September 28, 2017

まとめ

低頻度のCGダイヌクレオチドの抑制はHIV-1複製に不可欠です. このウイルスのゲノム適応は,CGに富んだRNAを標的とする宿主抗ウイルスタンパク質ZAPを回避するのに役立ちます.

科学分野:

ウイルス学
ゲノミクス
分子生物学

背景:

脊椎動物のゲノムはC-T変異によるCG抑制を示している.
多くの脊椎動物RNAウイルスはこのCG抑制を模倣しますが,その理由は不明です.
CG抑制はウイルスRNAに対する宿主の防御メカニズムです.

研究の目的:

HIV-1複製におけるCG抑制の役割を調査する.
CG抑制ウイルスRNAの認識に関与する宿主因子を特定する.
HIV-1が宿主の抗ウイルスメカニズムを回避する方法を理解するために

主な方法:

HIV-1におけるCGダイヌクレオチドの頻度を変化させる同義的な変異.
異なるCG含有量を持つ細胞におけるHIV-1の複製効率の評価
抗ウイルス因子を特定するための小型の抑制性RNAスクリーニング.
クロスリンク・イムノプレシピテーション・シーケンシング (CLIP-seq) で,RNAとタンパク質の相互作用を検出する.

主要な成果:

CG抑制はHIV-1の効率的な複製に不可欠です.
HIV-1 RNAのCG二核酸の増加は,複製の欠陥と細胞質RNAの枯渇につながります.
亜鉛指抗ウイルスタンパク質 (ZAP) はCG濃縮HIV-1の複製を阻害する.
ZAPはRNAのCGダイヌクレオチドに直接結合し,非自己として識別する.

結論:

HIV-1のCG抑制は,ZAP媒介の抗ウイルス防御を回避するための適応です.
ウイルスゲノムは宿主の免疫を回避するために特定のダイヌクレオチド組成を進化させることがあります.
ZAPは,自己RNAと非自己RNAを区別するための分子シグネチャーとしてCGダイヌクレオチド含有物を利用します.

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