细胞转录组的阿尔法疹病毒介导的重塑导致含有m6A的转录物耗尽
Robert J J Jansens1,2, Anthony Olarerin-George2, Ruth Verhamme1
1Department of Translational Physiology, Infectiology and Public Health.
iScience
|August 14, 2023
概括
病毒在感染期间通过N6-甲基氨酸 (m6A) 修饰选择性地减少宿主信使RNA (mRNA). 这种病毒免疫逃避策略依赖于YTHDF蛋白质,并影响抗病毒反应.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 对于调节宿主基因表达的病毒感染机制尚未完全理解.
- 编码抗病毒蛋白的宿主转录可以含有N6-甲基氨酸 (m6A) 修改.
- m6A在宿主病毒相互作用中的作用需要进一步研究.
研究的目的:
- 研究不同病毒如何影响含有m6A.的宿主转录.
- 确定病毒感染期间m6A修饰转录的选择性下调的基础机制.
- 探索这一法规对病毒免疫规避的影响.
主要方法:
- 在感染各种病毒后对宿主转录组进行系统分析.
- 专注于alphaherpesvirus (伪疹病毒和单纯疹病毒1) 来研究m6A修饰的转录调节.
- 研究YTHDF m6A结合蛋白的作用及其对P体的局部化.
- 在初级细胞中对YTHDF蛋白进行淘汰实验.
主要成果:
- 在感染仙台病毒,非洲猪瘟病毒,HSV-1和PRV期间观察到m6A甲基化转录的选择性下调.
- PRV和HSV-1对含有m6A的转录的下调取决于YTHDF蛋白质.
- YTHDF蛋白质定位到扩大的P体与转录下调相关.
- YTHDF蛋白倒退降低了PRV蛋白表达,并增强了抗病毒干扰素刺激的基因.
结论:
- 病毒采用一种策略,在感染期间耗尽宿主m6A修饰的转录.
- 这种枯竭是由YTHDF蛋白质调解的,并有助于病毒免疫逃避.
- 了解这种机制可以了解宿主-病原体相互作用和抗病毒防御.
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