伪狂犬病病毒体蛋白US2通过准cGAS-STING信号通路来对抗抗病毒先天免疫力
Zhengjie Kong1, Xing Chen2, Lele Gong2
1School of Advanced Agricultural Sciences, Peking University, Beijing, China.
Frontiers in immunology
|July 17, 2024
概括
伪狂热病毒 (PRV) 蛋白US2通过降解关键的抗病毒蛋白STING来逃避宿主免疫力. 这一发现解释了疫苗的失败,并建议US2作为新的PRV疫苗的目标.
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:
- 循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径对于抗病毒防御DNA病毒至关重要.
- 伪狂热病毒 (PRV) 采用各种策略来抵消宿主抗病毒免疫力.
- 关于PRV蛋白质在多大程度上逃避cGAS-STING通路的特征在很大程度上尚不清楚.
研究的目的:
- 研究PRV体膜蛋白US2在逃避cGAS-STING介导的I型干扰素抗病毒途径中的作用.
- 阐明PRV US2干扰STING信号的机制.
主要方法:
- 使用了稳定表达US2的细胞系和US2缺乏的PRV模型.
- 研究了PRV US2和STING之间的相互作用.
- 评估了E3结合酶TRIM21在US2介导的STING降解中的作用.
- 在小鼠模型中评估了US2缺乏对PRV毒性的影响.
主要成果:
- 发现PRV体膜蛋白US2降低了STING蛋白的稳定性,从而降低了STING介导的抗病毒信号.
- US2通过招募E3结合酶TRIM21促进STING降解,从而导致K48结合的无处不在.
- 缺乏TRIM21增强了宿主对PRV感染的抗病毒反应,而缺乏US2的PRV在小鼠中表现出减少的毒性.
结论:
- PRV US2通过一种针对STING蛋白稳定的新机制抑制干扰素信号传递,有效地逃避宿主抗病毒反应.
- 这项研究揭示了一种新的PRV免疫规避策略,并解释了某些PRV疫苗对变种菌株的有效性有限.
- PRV US2代表了开发新型基因缺陷PRV疫苗的潜在目标.
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