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FTSJ3是一个由HIV招募的RNA2'-O-甲基转移酶,以避免先天的免疫感应
Mathieu Ringeard1, Virginie Marchand2, Etienne Decroly3
1IGH, CNRS, Université de Montpellier, Montpellier, France.
Nature
|January 11, 2019
概括
通过将TRBP-FTSJ3复合物引入病毒RNA,使HIV-1逃避免疫检测. 这种复合物通过2'- O- 甲基化修改病毒RNA,防止先天免疫系统识别它,并减少1型干扰素的产生.
科学领域:
- 分子生物学
- 免疫学
- 病毒学
背景情况:
- 哺乳动物的先天免疫通过2O甲基化来区分自我与非自我RNA.
- 精确的RNA2-O甲基化的分子功能在很大程度上是未知的.
- 艾滋病毒-1利用策略来逃避宿主免疫反应.
研究的目的:
- 阐明RNA2-O甲基化的分子功能.
- 确定HIV-1逃避天生的免疫识别的机制.
- 研究TRBP-FTSJ3复合体在HIV-1RNA修饰中的作用.
主要方法:
- 净化TARRNA结合蛋白 (TRBP) 和相互作用的合作伙伴.
- 在体外和体外生化测试.
- 用于确定RNA甲基化位点的RiboMethSeq分析.
- 在产生HIV-1的细胞中进行FTSJ3淘汰实验.
- 在人体树突细胞中进行1型干扰素诱导试验.
主要成果:
- 鉴定了一种含有FTSJ3的DICER独立的TRBP复合物,一种2 -O-甲基转移酶 (2'-O-MTase).
- 通过TRBP,FTSJ3被招募到HIVRNA中,并在病毒基因组中调解特定的2-O-甲基化.
- 在FTSJ3淘汰细胞中产生的HIV-1呈现了降低的2 -O-甲基化.
- 减少病毒RNA甲基化导致MDA5传感器的识别增加,并触发了1型干扰素 (IFN-α/ β) 的产生.
- 这种干扰素反应导致艾滋病毒的表达减少.
结论:
- 艾滋病毒-1采用了一种涉及TRBP-FTSJ3复合物的机制来对其RNA进行2 -O-甲基化,从而逃避MDA5的先天免疫检测.
- 这种病毒RNA修饰抑制了1型干扰素的诱导,促进了免疫逃避.
- 这项研究揭示了病毒RNA,宿主因子和先天免疫之间的新型相互作用,影响病毒复制和病变.
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