猪流行性腹病毒操纵IMPDH依赖的核酸生物合成,以促进复制
Shuting Zhou1, Houde Zhao1, Junrui Zhu2
1Shanghai Collaborative Innovation Center of Agri-Seeds / School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
Journal of virology
|January 9, 2026
概括
猪流行性腹病毒 (PEDV) 通过向氨酸单酸脱酶 (IMPDH) 来劫持宿主瓜诺辛生物合成. 抑制IMPDH减少PEDV复制,将其确定为猪健康的潜在抗病毒标.
科学领域:
- 病毒学 病毒学
- 代谢学 代谢学 代谢学
- 生物化学 生物化学
背景情况:
- 猪流行性腹病毒 (PEDV) 在猪中引起严重的肠道疾病,导致猪业的重大经济损失.
- 高发病率和死亡率,特别是在新生猪群中,强调迫切需要有效的控制策略.
- 了解代谢水平上的宿主-病原体相互作用对于开发新型治疗干预措施至关重要.
研究的目的:
- 通过使用非向的代谢概况来调查PEDV感染引起的宿主代谢变化.
- 确定PEDV利用其复制的关键宿主因素和代谢途径.
- 评估伊诺辛单酸脱酶 (IMPDH) 作为一种潜在的宿主导抗病毒向PEDV.
主要方法:
- 在感染PEDV的LLC-PK1 (猪) 和Vero E6 (灵长类动物) 细胞上进行了非向的代谢分析.
- 进行了途径丰富分析,以确定显著改变的代谢途径.
- 用merimepodib (MMPD) 来对IMPDH2进行基因淘汰和药理抑制,以评估IMPDH在PEDV复制中的作用.
主要成果:
- 在宿主细胞中,PEDV感染显著改变了核酸代谢,辅因子生物合成,氨基酸生物合成和 purin代谢.
- 观察到细胞特异性的纯素代谢调节,Vero E6细胞的上调和LCL-PK1细胞的下调在感染后18小时.
- 伊诺辛单酸脱酶 (IMPDH) 是关氨酸核酸生物合成中的限制速率酶,被确定为PEDV复制的必需品. IMPDH的遗传和药理抑制都抑制了病毒RNA水平和复制.
结论:
- PEDV劫持了依赖IMPDH的瓜诺辛生物合成途径,以促进其复制.
- IMPDH代表了PEDV的关键宿主依赖因素.
- 针对IMPDH提供了一个有前途的宿主导抗病毒策略,用于控制猪中PEDV感染.
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