盖莱克3结合蛋白抑制PRRSV复制通过Cullin3介导的非结构蛋白12的泛基化降解
Xinrong Wang1, Wenli Zhang1, Juan Zhang1
1College of Veterinary Medicine, Southwest University, Chongqing, China.
Journal of virology
|October 15, 2025
概括
素3结合蛋白 (LGALS3BP) 通过降解病毒蛋白nsp12来抑制猪生殖和呼吸系统综合征病毒 (PRRSV). 这种宿主因子还能增强先天免疫力,提供对PRRSV的双重策略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 猪生殖和呼吸系统综合征病毒 (PRRSV) 显著影响全球猪产量.
- 由于PRRSV的遗传多样性和免疫逃避,对于PRRSV存在有限的有效抗病毒策略.
- 病毒非结构蛋白12 (nsp12) 对于PRRSVRNA合成至关重要,并且高度保守.
研究的目的:
- 为了确定抑制PRRSV感染的宿主因素.
- 阐明LGALS3BP限制PRRSV复制的机制.
- 探索LGALS3BP作为针对PRRSV的治疗点的潜力.
主要方法:
- 研究了加列3结合蛋白 (LGALS3BP) 在PRRSV感染中的作用.
- 利用基因过度表达和淘汰技术来评估LGALS3BP对病毒复制的影响.
- 为了确定作用机制,采用了全方位化试验和蛋白质体降解研究.
- 分析了LGALS3BP对宿主天生的免疫反应的影响,包括干扰素途径.
主要成果:
- 鉴定出LGALS3BP是一种抑制PRRSV复制的宿主因子.
- LGALS3BP针对保存的病毒nsp12蛋白进行ubiquitination和proteasomal降解.
- 过度表达LGALS3BP抑制了病毒复制,而敲击则增强了病毒复制.
- 此外,LGALS3BP还提高了干扰素β和干扰素刺激基因的调节,从而提高了先天免疫力.
- 在不同的PRRSV菌株中观察到LGALS3BP的抗病毒活性.
结论:
- LGALS3BP通过双重机制抑制PRRSV:直接降解nsp12并增强宿主天生的免疫力.
- 在控制猪中PRRSV感染方面,LGALS3BP是一个有前途的治疗标.
- 了解宿主-病原体相互作用,如LGALS3BP-PRRSV轴,是开发新型抗病毒策略的关键.
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