伪狂热病毒感染激活了NLRP3和IFI16炎症体,从而触发了热致死
Xiaohua Zhang1, Guiyuan Chen1, Junqing Yin1
1College of Veterinary Medicine, Northwest A&F University, Yangling, China.
Veterinary microbiology
|July 8, 2023
概括
伪狂犬病病毒 (PRV) 在猪中引发气皮素D (GSDMD) 介导的热,涉及NLRP3和IFI16炎症体. 这种细胞死亡途径对于理解PRV病原体和开发治疗方法至关重要.
科学领域:
- 兽医病毒学 兽医病毒学
- 免疫学 免疫学 免疫学
- 细胞病理学细胞病理学
背景情况:
- 伪狂热病毒 (PRV) 在猪中引起重大疾病,影响神经和其他组织.
- 热,一种编程细胞死亡的形式,由炎症性体和炎症体介导.
- 在其自然宿主中,PRV诱导的热的机制需要进一步阐明.
研究的目的:
- 为了研究猪细胞中PRV诱导的火灭的机制.
- 为了确定在PRV感染中涉及的炎细胞和细胞死亡途径.
- 为了将体外发现与在感染PRV的猪中观察到的结果相对应.
主要方法:
- 猪膜巨细胞感染了PRV.
- 对热灭菌标记物的分析,包括气体皮质D (GSDMD) 裂变,IL-1β分泌和乳酸脱酶 (LDH) 释放.
- 评估炎症酶激活 (NLRP3,IFI16),卡斯帕酶-1活性,反应性氧物种 (ROS) 生产和流量.
- 对感染PRV的猪组织 (大脑,肺) 进行关键分子标记物的检查.
主要成果:
- 在猪细胞中,PRV感染诱导了GSDMD介导的,而不是GSDME介导的Pyroptosis.
- 卡斯巴酶-1激活对于GSDMD裂变至关重要,并且需要病毒复制/蛋白质生产来进行热.
- PRV触发了NLRP3和IFI16炎症酶的激活,这些激活对热症至关重要.
- NLRP3炎症酶激活与ROS产生和流量有关.
- 在体内,受PRV感染的组织显示了GSDMD裂变,活化caspase-1,以及NLRP3和IFI16水平升高.
结论:
- 在猪中,PRV感染通过NLRP3和IFI16炎症酶激活了GSDMD依赖的火灭菌.
- 病毒复制和蛋白质合成是诱导这种细胞死亡途径所必需的.
- 了解这些机制,可以深入了解PRV病原体和潜在的治疗策略.
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