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胚胎干细胞使用ZFP809来沉默复原病毒DNA

Daniel Wolf¹, Stephen P Goff

¹Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, HHSC 1310, 701 West 168th Street, New York, New York 10032, USA.

|March 10, 2009

概括

指蛋白ZFP809作为干细胞防御逆转录病毒. 它识别集成的逆转录病毒DNA,招募TRIM28,并沉默病毒复制,保护干细胞和潜在的其他细胞免受感染.

科学领域:

分子生物学分子生物学
病毒学病毒学
干细胞生物学干细胞生物学
免疫学免疫学免疫学

背景情况:

胚胎干细胞 (ESC) 具有强大的阻断逆转录病毒复制的能力,这种机制活跃了30多年.
鼠类白血病病毒 (MLVs) 集成到ESC DNA中,但被转录性沉默,防止病毒传播.
这种沉默涉及到识别初始结合位 (PBS) 的转作用因子,这是一个与特定转移RNA (tRNA) 互补的序列.

研究的目的:

确定负责识别集成逆转录病毒DNA和招募TRIM28用于ESC中的转录沉默的特定因素.
研究该因子在干细胞和分化细胞中对逆转录病毒感染的抗性中介作用.

主要方法:

确定ZFP809是与TRIM28复合的蛋白质,该蛋白质位于综合性前病毒DNA的原始结合部位.
评估ZFP809表达能否在分化细胞中赋予MLV感染的抗性.
评估ZFP809对人类T细胞淋巴细胞病毒-1 (HTLV-1) 构造物的转录的影响.

主要成果:

指蛋白ZFP809被确定为桥梁集成逆转录病毒DNA和TRIM28.28的分子.
仅ZFP809的表达就足以在分化的细胞中赋予MLV感染的高耐药性.
ZFP809有效地阻止了使用相同的原始tRNA的HTLV-1DNA结构的转录.

结论:

ZFP809是一种DNA结合因子,专门识别了哺乳动物逆转录病毒和逆元件的重要子集.
ZFP809针对这些逆转录病毒序列进行转录沉默,作为干细胞中的新型内在免疫因子.
ZFP809作为干细胞特异性的逆转录病毒限制因子,有助于干细胞的先天防御机制.

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