伪狂犬病病毒UL4蛋白促进ASC依赖的炎症酶激活和热,加剧炎症
Xiaohua Zhang1, Guiyuan Chen1, Junqing Yin1
1College of Veterinary Medicine, Northwest A&F University, Yangling, China.
PLoS pathogens
|September 24, 2024
概括
伪狂犬病病毒蛋白UL4增强了炎症酶激活和热,增加了疾病的严重程度. 准UL4可能会导致针对伪狂犬病的新疗法.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 伪狂热病毒 (PRV) 通过炎症酶激活和热死引起炎症和组织损伤.
- 驱动这些宿主反应的精确病毒机制仍然不完全理解.
研究的目的:
- 阐明PRV非结构性蛋白UL4在炎症酶激活和热致死中的作用.
- 调查UL4作为针对PRV的治疗干预的潜在目标.
主要方法:
- 研究了PRV UL4与ASC (含有CARD的与亡相关的斑状蛋白) 的相互作用.
- 分析了UL4对NLRP3和AIM2炎症酶激活,SYK和JNK酸化以及ASC寡合化的作用.
- 利用与PRV UL4突变菌株 (PRV-UL4mut) 的体内实验来评估病原性和炎症标志物.
主要成果:
- PRV UL4 直接增强了依赖ASC的炎症酶激活和烧灭.
- UL4转移到细胞质,与ASC相互作用,并通过SYK/JNK信号传递促进NLRP3/AIM2炎症酶激活.
- PRV-UL4mut感染导致IL-1β,IL-18,GSDMD-NT水平降低,肺/大脑病理和死亡率减弱.
结论:
- PRV UL4 是一个关键的病毒调节器,它操纵宿主炎症体信号和热,以促进PRV的致病性.
- UL4代表了开发活体减弱疫苗或针对伪狂犬病的新疗法战略的有希望的目标.
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