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膜蛋白CRISPR屏幕识别了RPSA作为猪流行性腹病毒复制的重要宿主因素

Yu Zhao¹, Guanghao Guo¹, Yumei Sun¹

¹National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Journal of virology

|July 30, 2025

概括

核糖体蛋白SA (RPSA) 是猪流行性腹病毒 (PEDV) 复制的关键宿主因素,而不是入口. 它的缺失通过降低ERK1/2通路的调节和影响脂质新陈代谢来损害病毒复制,提供新的抗病毒标.

科学领域:

病毒学病毒学
分子生物学分子生物学
宿主-病原体相互作用

背景情况:

猪流行性腹病毒 (PEDV) 在全球猪业造成重大损失.
对于PEDV复制必不可少的宿主因素,包括病毒受体,尚不清楚.
猪肠道冠状病毒 (SeCoVs) 构成经济和公共卫生风险.

研究的目的:

使用CRISPR/Cas9屏幕识别PEDV复制所需的宿主因素.
为了研究核糖体蛋白SA (RPSA) 在冠状病毒感染中的作用.
探索RPSA对病毒复制,宿主信号通路和细胞代谢的影响.

主要方法:

开发了一个猪膜蛋白规模的CRISPR/Cas9淘汰 (PigMpCKO) 库.
在猪细胞中进行了两轮PEDV感染.
使用了抑制剂/激活剂实验,RNA测序和机械学研究.

主要成果:

确定RPSA作为PEDV复制的关键宿主因素,而不是入口.
证明RPSA淘汰抑制ERK1/2通路,从而影响PEDV感染.
观察到抑制脂质生物合成和运输,降低RPSA淘汰细胞中的胆固醇和甘油三水平.
发现RPSA淘汰也可以抑制传染性胃肠炎病毒 (TGEV) 和猪三角冠状病毒 (PDCoV) 感染.

结论:

RPSA是一种新型宿主因子,对多种猪肠道冠状病毒的复制至关重要.
RPSA通过ERK1/2途径调节病毒复制,并影响细胞脂质代谢.
这些发现为病毒与宿主相互作用以及潜在的广泛抗病毒治疗点提供了洞察力.

关键词:

这就是CRISPR/Cas9的作用.通过ERK1/2路径.猪流行性腹病毒病毒在 RPSA 中使用 RPSA.氨基胺酶 N 种子脂质新陈代谢脂质新陈代谢

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