周围神经系统受到寨卡病毒非结构性 (NS) 蛋白-1引起的中性粒细胞外陷 (NET) 的伤害
Raphael de Siqueira Santos1, Natalia Cadaxo Rochael2, Thayana Roberta F Mattos2
1Laboratório de Agregação de Proteínas e Amiloidoses, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
概括
寨卡病毒 (ZIKV) 非结构蛋白1 (NS1) 触发中性粒细胞外细胞陷 (NETs),这些陷会损害外周神经. 这一发现揭示了一个新的ZIKV神经炎症途径,涉及NETs和MPO.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 病毒学 病毒学
背景情况:
- 天生的免疫在寨卡病毒 (ZIKV) 神经炎症中的作用尚不清楚.
- 中性细胞外细胞陷 (NETs) 是涉及组织损伤的DNA-蛋白质支架.
研究的目的:
- 为了研究NETs在ZIKV感染期间损害外周神经的潜力.
- 为了确定ZIKV诱导的神经炎症的机制.
主要方法:
- NETs被添加到背部根腺 (DRG) 扩展体和细胞中,或注射到小鼠的坐骨神经中.
- 药理抑制发现了有害的NET组件.
- 使用ZIKV及其NS1蛋白来评估NET形成和毒性.
主要成果:
- 齐克病毒感染诱导了中性粒细胞的招募和诱导NET的细胞因子,但不是NET.
- ZIKV NS1蛋白,但不是ZIKV本身,诱导了NET的形成.
- NET对DRG扩增剂和髓化细胞有毒,MPO和基因组被确定为有害成分.
- 在体内,NS1和MPO注射诱导了NET释放,中性粒细胞招募和caspase-3激活.
结论:
- ZIKV NS1蛋白诱导NET的形成,导致外周神经系统受损.
- NETs,特别是MPO,是ZIKV诱导的神经炎症的关键调解者.
- 这项研究揭示了ZIKV病变的新型机制.
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