通过内生逆转录病毒的选择来调节先天免疫的演变
Edward B Chuong1, Nels C Elde2, Cédric Feschotte2
1Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
概括
内源逆转录病毒 (ERV) 通过提供新的转录增强剂来形成哺乳动物的免疫防御. 这些病毒序列对于天生的免疫力和基因创新至关重要.
科学领域:
- 基因组学
- 免疫学
- 进化生物学
背景情况:
- 内源逆转录病毒 (ERV) 在哺乳动物基因组中普遍存在,并且具有转录调节元素.
- 在基因调节的演变中ERV传播的作用尚不清楚.
研究的目的:
- 研究ERVs对基因调节的演变的影响,特别是在干扰素 (IFN) 反应网络中.
- 确定ERV衍生增强剂在哺乳动物先天免疫中的功能意义.
主要方法:
- 进行比较基因组学以识别血统特异性的ERV及其分布.
- 在人体细胞中编辑CRISPR-Cas9基因以删除ERV元素.
- 对IFN刺激和炎症酶激活的基因表达变化的分析.
主要成果:
- 在不同哺乳动物血统中,ERVs显著影响了IFN响应转录网络的演变.
- 特定系的ERV已经独立分散了许多IFN诱导增强剂.
- 人类中ERV元素的删除损害了IFN诱导基因的表达,并影响了AIM2炎症酶的激活.
结论:
- 作为调节序列的储存器,ERV可增强先天免疫系统对干扰素的反应.
- 这些古老的病毒元素有助于基因创新和哺乳动物免疫防御的进化.
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