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人类细胞巨头病毒长非编码RNA抵制核cGAS以促进免疫逃避

Sungwon Lee^1,2, Sungchul Kim^1,3, Hyejun Kim^1,2

¹Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.

Nature microbiology

|August 8, 2025

概括

人类细胞巨核病毒 (HCMV) 使用一种非编码RNA,RNA4.9,来抑制宿主.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

病毒采用免疫逃避策略,经常准宿主模式识别受体.
病毒非编码RNAs在调节这些受体中的功能在很大程度上是未知的.

研究的目的:

研究人类细胞巨乳病毒 (HCMV) 编码的非编码RNAs在调节宿主免疫反应中的作用.
为了确定病毒非编码RNA是否可以干扰模式识别受体信号通路.

主要方法:

鉴定和特征HCMV长非编码RNA4.9.9.
评估RNA4.9与宿主循环GMP-AMP合成酶 (cGAS) 之间的相互作用.
使用反感性寡核酸来阻断RNA4.9功能,并观察病毒复制和cGAS活性的影响.

主要成果:

HCMV产生RNA4.9,一个长的非编码RNA,抑制核cGAS介导的免疫反应.
RNA4.9与cGAS结合,减少其酶活性和下游干扰素的产生,从而促进病毒复制.
用反感性寡核酸阻断RNA4.9的结构恢复了cGAS活性,并阻碍了病毒复制.
在 HCMV DNA 附近的RNA4.9定位与有效的cGAS抑制和免疫抑制相关.

结论:

病毒非编码RNA,如HCMVRNA4.9,是cGAS通路的关键调节者.
RNA4.9通过抑制宿主天生的免疫力来促进病毒感染.
病毒非编码RNAs代表抗病毒策略的潜在治疗点.

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