VLDLR和ApoER2是多个α病毒的受体
Lars E Clark1, Sarah A Clark1, ChieYu Lin1
1Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nature
|December 20, 2021
概括
非常低密度脂蛋白受体 (VLDLR) 作为阿尔法病毒的关键受体,使其能够在不同的宿主中感染. 这一发现为阿尔法病毒疾病提供了潜在的治疗点.
科学领域:
- 病毒学
- 分子生物学
- 进化生物学
背景情况:
- 阿尔法病毒是关节动物传播的病毒,具有广泛的宿主范围,感染脊椎动物和无脊椎动物.
- 了解阿尔法病毒进入宿主细胞的机制至关重要,因为宿主物种之间的受体可能有很大差异.
- 之前的研究发现了各种阿尔法病毒受体,但很少存在于脊椎动物和无脊椎动物宿主中.
研究的目的:
- 识别阿尔法病毒进入宿主细胞所使用的保存细胞受体.
- 研究非常低密度脂蛋白受体 (VLDLR) 和阿波脂蛋白E受体2 (ApoER2) 在阿尔法病毒感染中的作用.
- 探索针对这些受体的治疗干预对抗α病毒感染的潜力.
主要方法:
- 确定VLDLR是一个Semliki森林病毒受体.
- 病毒糖蛋白 (E2- E1) 与VLDLR和ApoER2的配体结合域 (LBD) 之间的相互作用已被证明.
- 在细胞培养模型 (人类和小鼠神经元) 中利用了子宫外表达,病毒样颗粒和受体阻断融合蛋白/对手.
- 在小鼠新生儿模型中评估了VLDLR LBD-Fc融合蛋白的体内保护作用.
- 在无脊椎动物物种 (蚊子,虫) 中研究了功能性阿尔法病毒受体.
主要成果:
- VLDLR被确定为Semliki森林病毒的功能受体.
- 来自Semliki森林病毒,东方马脑炎病毒和Sindbis病毒的病毒糖蛋白E2-E1与VLDLR和ApoER2 LBDs结合.
- 在子宫外表达VLDLR或ApoER2促进了阿尔法病毒的附着和内化.
- 一种VLDLR LBD-Fc融合蛋白和一种联体结合抗体阻断了培养的神经元中的α病毒感染.
- 在小鼠中,使用VLDLR LBD- Fc融合蛋白对Semliki森林病毒产生保护作用.
- 无脊椎动物的VLDLR基因作为阿尔法病毒受体.
结论:
- 非常低密度脂蛋白受体 (VLDLR) 是多个α病毒的关键细胞受体,包括Semliki森林病毒.
- 多种宿主之间的阿尔法病毒传染性可能由维护脂蛋白受体 (如VLDLR) 介导.
- 针对VLDLR是一个有前途的治疗策略来治疗alphavirus感染.
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