脳幹ウイルス感染症のヒトにおけるRNAラリアト代謝の先天性エラー
Shen-Ying Zhang1, Nathaniel E Clark2, Catherine A Freije3
1St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris 75015, France; Paris Descartes University, Imagine Institute, Paris 75015, France.
Cell
|February 24, 2018
まとめ
DBR1遺伝子の変異は,RNA lariat分岐酵素の欠乏を引き起こし,子供に重度の脳幹感染症を引き起こす. この遺伝的欠陥は HSV1のようなウイルスに対する 身体の自然な防御を損なうのです
科学分野:
- 遺伝学
- ウイルス学
- 免疫学
背景:
- 無害なウイルスは 健康な子供の脳幹に感染します
- DBR1遺伝子はRNA処理に不可欠なRNA lariat分岐酵素をコードする.
研究 の 目的:
- 再発性脳幹感染症の遺伝的根拠を調査する.
- ウイルス感受性と脳幹免疫における DBR1 の役割を決定する.
主な方法:
- DBR1の変異を特定するための遺伝子解析
- RNA lariatレベルとウイルス感受性を評価するために,患者の線維芽細胞を用いた細胞測定法.
- 異なる組織におけるDBR1発現パターンの分析
主要な成果:
- 関連性のない脳幹感染症患者の双アレル DBR1 変異を特定した.
- DBR1変異は,発現と機能が低下した重度の低形性アレルをもたらした.
- DBR1欠乏した線維細胞は,RNAラリアトの蓄積が増加し,HSV1感染に対する感受性が高まった.
- 野生型DBR1が患者の細胞に蓄積し,ウイルスの感受性を回復させた.
結論:
- オートソームリセッシブ部分的なDBR1欠乏症は組織特異的免疫を乱し,個人を重度の脳幹ウイルス感染症に誘発する.
- DBR1は,特に脳幹におけるウイルスに対する細胞内在の免疫において重要な役割を果たします.
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