通过FUT1和GAL3ST2介导的细胞甘氨酸重塑大大限制了依赖酸的病毒感染
Xinyu Zhu1, Satoko Nakano1, Vishwas N Rao1
1Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710.
概括
通过抑制fucosyltransferase 1 (FUT1) 和galactose-3-O-sulfotransferase 2 (GAL3ST2),通过减少细胞表面酸,抑制病毒感染. 这些酶作为宿主限制因子,提供广泛的抗病毒策略.
科学领域:
- 病毒学 病毒学
- 葡萄糖生物学 葡萄糖生物学
- 分子生物学分子生物学
背景情况:
- 酸是许多病毒用于附着和进入的关键细胞表面甘氨酸.
- 改变细胞糖化对病毒感染的易感性产生影响,但缺乏对糖封闭酶的系统分析.
研究的目的:
- 系统地分析改变终端甘氨酸封闭酶对病毒感染率的影响.
- 识别特定的糖转移酶,可以抑制广泛的酸依赖病毒.
主要方法:
- 一个阵列的CRISPR激活屏幕,针对54个参与终端甘氨酸修饰的甘氨酸转移酶.
- 评估细胞系的敏感性,改变了12种不同病毒的酶表达.
- 利用莱克和病毒颗粒结合试验来研究抑制的机制.
- 通过在各种细胞模型中使用腺相关病毒传递来证实抑制作用,包括人类初级呼吸道细胞.
主要成果:
- 基转移酶1 (FUT1) 和银河糖-3-O-硫转移酶2 (GAL3ST2) 在上调时被确定为宽谱病毒感染的抑制剂.
- 这些酶通过分别化和硫化减少了细胞表面α2-3和α2-6化.
- 观察到病毒附着功能受损,这表明初始进入过程的减少.
- 在多种细胞类型中证实了流感病毒的抑制作用,包括人类呼吸道细胞.
结论:
- FUT1和GAL3ST2作为对各种病毒的宿主限制因子.
- 对FUT1和GAL3ST2的治疗性失调是一种潜在的广泛的抗病毒策略.
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