HSP90AB1是一种促进猪三角型冠状病毒复制的宿主因子
Yujia Zhao1, Jianlin Yuan2, Dai Xiao2
1Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China; Laboratory Animal Center, Zunyi Medical University, Zunyi, China.
The Journal of biological chemistry
|December 13, 2023
概括
热冲击蛋白90α家族B1类 (HSP90AB1) 促进猪三角型冠状病毒 (PDCoV) 感染. 抑制HSP90AB1显著抑制PDCoV,显示出一个潜在的抗病毒标.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 猪三角冠状病毒 (PDCoV) 是一种新兴的肠病原体病毒,导致小猪的显著死亡率.
- 广泛的PDCoV宿主范围,包括潜在的人类传播,加剧了其公共卫生问题.
- 导致PDCoV病变的确切机制在很大程度上仍未被阐明.
研究的目的:
- 通过全基因组的CRISPR屏幕来识别PDCoV感染所必需的宿主因素.
- 研究热冲击蛋白90α家族B1类 (HSP90AB1) 在PDCoV复制中的作用.
- 探索HSP90AB1作为PDCoV抗病毒策略的潜在治疗标.
主要方法:
- 在感染PDCoV的LLC-PK细胞中进行全基因组CRISPR查.
- 基因淘汰和淘汰 (KO) 的HSP90AB1.1.
- 用特定的HSP90抑制剂治疗受感染细胞 (17-AAG,VER-82576,KW-2478).
- 同免疫沉测试以确定蛋白质相互作用.
- 西部斑点分析以评估蛋白质的稳定性.
主要成果:
- HSP90AB1被确定为促进PDCoV感染的关键宿主因素.
- HSP90AB1淘汰或KO显著抑制了PDCoV复制.
- HSP90抑制剂17-AAG和VER-82576有效抑制了PDCoV感染,而KW-2478没有.
- 发现HSP90AB1与PDCoV N,NS7和NSP10蛋白相互作用,特别是N蛋白的C尾域.
- HSP90AB1保护PDCoV N蛋白质免受蛋白质体的降解.
结论:
- HSP90AB1通过稳定病毒N蛋白在PDCoV生命周期中发挥关键作用.
- 准HSP90AB1为控制PDCoV感染提供了一个有希望的治疗策略.
- 这项研究为PDCoV的宿主病毒相互作用提供了新的见解,为新型抗病毒开发铺平了道路.
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