病毒进入和转化到大脑内皮细胞中,引发流感相关脑病变
Shihoko Kimura-Ohba1,2,3,4, Mieko Kitamura5, Yusuke Tsukamoto6,5
1Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan. skimura@virus.med.osaka-u.ac.jp.
Acta neuropathologica
|April 30, 2024
概括
流感相关脑病变 (IAE) 是由流感A病毒 (IAV) 感染大脑内皮细胞引起的. 病毒RNA的转录和翻译,而不是扩散,驱动IAE的病变和致命性.
科学领域:
- 神经病毒学 神经病毒学
- 病理学 病理学 病理学
- 传染性疾病 传染性疾病
背景情况:
- 流感相关脑病变 (IAE) 呈现出迅速发病,高死亡率和未知的急性阶段脑病原体.
- 在IAE急性阶段,流感病毒在大脑中的直接作用在很大程度上仍未被阐明.
研究的目的:
- 研究导致IAE的大脑中A型流感病毒 (IAV) 的直接致病性.
- 确定IAV诱导脑病变的细胞点和机制.
主要方法:
- 年轻小鼠被IAV接种,神经学得分,组织病理学和病毒研究在接种后的72小时内进行.
- 人类IAE尸检大脑被通过组织病理学检查.
- 用内皮细胞和天体细胞系来分析病毒感染,增殖和病变发生.
- 抗流感药物的疗效在细胞系和动物模型中进行了评估.
主要成果:
- 在小鼠的IAV接种导致脑病变,脑,微型出血和星球细胞损伤在72小时内.
- 病毒核蛋白在小鼠和人类IAE患者的脑内皮细胞中被检测到感染后24小时.
- 被IAV感染的内皮细胞显示病毒蛋白沉积和细胞死亡,病毒放大程度有限.
- 抑制病毒转录/翻译减少了内皮细胞死亡和小鼠模型死亡率.
结论:
- 由IAV感染的大脑内皮细胞是IAE发作的可能原因.
- IAV进入内皮和随后的病毒RNA转录/翻译,而不是病毒复制,是IAE的关键致病机制.
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