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DNA腫瘍ウイルスの腫瘍遺伝子は,cGAS-STING DNA感知経路を阻害する
Laura Lau1, Elizabeth E Gray1, Rebecca L Brunette1
1Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Science (New York, N.Y.)
|September 26, 2015
まとめ
HPVのようなDNA腫瘍ウイルスの腫瘍遺伝子
科学分野:
- 免疫学
- ウイルス学
- 分子生物学
背景:
- 循環グアノシン・モノフォスファート・アデノシン・モノフォスファート合成酵素 (cGAS) は,細胞内DNAを検出し,STING経路経由で抗ウイルス反応を開始するために重要である.
- cGAS-STING経路を回避または阻害するDNAウイルスの能力は十分に理解されていません.
研究 の 目的:
- DNA腫瘍ウイルスが cGAS-STING DNA感知経路を阻害するタンパク質をコードするかどうかを調査する.
- この先天的な免疫経路を阻害する特定のウイルス性オンコタンパク質を特定する.
主な方法:
- cGAS-STING経路活動に関連したウイルス腫瘍遺伝子の発現分析
- ウイルスのオンコタンパク質とSTINGの相互作用を決定する生化学的測定.
- ヒトの腫瘍細胞での遺伝子静止実験で 経路の回復を評価する
主要な成果:
- ヒトパピローマウイルス (HPV) のウイルス性オンコタンパク質E7とアデノウイルスからのE1Aは,cGAS- STING経路の強力な阻害剤として特定されました.
- これらのオンコプロテイン内のLXCXEモチーフは,レチノブラストームの腫瘍抑制剤と結合することが知られているが,DNAセンシングを反発させるには極めて重要です.
- E1AとE7はSTINGに直接結合し,腫瘍細胞の静止はcGAS-STING経路を再活性化します.
結論:
- DNA腫瘍ウイルスのウイルス腫瘍遺伝子は,cGAS-STINGによって媒介される宿主の先天的な抗ウイルス防御を積極的に抑制する.
- このウイルスの対立は,宿主ウイルスとの進化的対立を強調し,ウイルスの腫瘍遺伝子の進化を促す可能性がある.
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