感染诱导的氨酸乳酸化使得疹病毒的免疫逃避成为可能
Matthew D Tyl1, Victoria U Merengwa1, Ileana M Cristea1
1Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Science advances
|January 8, 2025
概括
病毒感染劫持乳酸来修改蛋白质,抑制免疫反应并帮助传播. 这项研究揭示了人类细胞巨乳病毒 (HCMV) 如何利用蛋白质乳糖化来逃避免疫.
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:
- 有氧糖解和乳酸积累在病毒感染中很常见.
- 乳酸在调节病毒病原发生的具体作用尚不清楚.
研究的目的:
- 调查乳酸在病毒感染中的作用,特别是人类细胞巨乳病毒 (HCMV).
- 探索乳酸如何影响感染期间的蛋白质修饰和免疫信号.
主要方法:
- 分析HCMV感染细胞中的蛋白质乳酸化.
- 乳酸蛋白及其功能域的识别.
- 研究乳糖化对免疫信号通路和病毒传播的影响.
主要成果:
- HCMV感染诱导了广泛的蛋白质乳糖化,特别是在内在无序的区域.
- 像RNA结合蛋白14和干扰素γ诱导蛋白16 (IFI16) 这样的免疫因子的乳化抑制了免疫反应.
- 在IFI16的K90的特定乳化抑制DNA-PK招募,阻断IFI16介导的病毒基因抑制和细胞因子的产生.
结论:
- 病毒诱导的乳酸盐通过诱导蛋白质乳化促进病毒的传播.
- 蛋白质乳化是病毒免疫逃避的一个关键机制,在HCMV和简单疹病毒1感染中观察到.
- 向蛋白质乳化可以提供针对病毒感染的新策略.
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