流感A病毒诱导的葡萄糖溶解通过激活ROS/HIF-1α通路来促进病毒复制
Yijia Zhang1, Lifeng Chang1, Xin Xin1
1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Free radical biology & medicine
|November 4, 2024
概括
流感A病毒感染促进宿主细胞糖解,通过ROS/HIF-1α途径增加病毒复制. 糖解抑制剂减少了小鼠的病毒载量和肺损伤,这表明了新的治疗点.
科学领域:
- 病毒学 病毒学
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- A型流感病毒 (A/WSN/1933) 是一种具有重大公共卫生影响的传染性呼吸道疾病.
- 流感A病毒复制对宿主细胞葡萄糖代谢的依赖已知,但具体机制尚不清楚.
研究的目的:
- 为了研究流感A病毒感染对宿主细胞葡萄糖代谢的影响.
- 阐明这些代谢变化背后的分子机制及其在病毒复制中的作用.
主要方法:
- 创建WSN病毒感染的小鼠和A549细胞模型.
- 对代谢学和转录学数据的分析.
- 在体内对糖解抑制剂 (2-脱氧葡萄糖) 和HIF-1α抑制剂 (PTX-478) 的评估.
主要成果:
- 在A549细胞中,WSN病毒感染上调了糖解,由增高的hexokinase 2 (HK2),乳酸脱酶A (LDHA),缺氧诱导因子-1α (HIF-1α) 和乳酸水平表明.
- 观察到线粒体功能障碍和高反应性氧物种 (ROS).
- 在小鼠中,抑制糖解或HIF-1α降低了WSN病毒复制,乳酸生产,体重减轻和肺损伤.
结论:
- 流感A病毒感染增强了葡萄糖分解,通过ROS/HIF-1α信号通路促进病毒复制.
- 向糖解或HIF-1α激活是对抗流感A病毒感染的潜在治疗策略.
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