Mxra8是多种关节致病性α病毒的受体
Rong Zhang1, Arthur S Kim1,2, Julie M Fox1
1Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Nature
|May 18, 2018
概括
研究人员确定Mxra8是关键的宿主因子. 在细胞培养和小鼠模型中,用阻断抗体或融合蛋白向Mxra8可减少病毒感染和疾病症状.
科学领域:
- 病毒学
- 免疫学
- 分子生物学
背景情况:
- 关节病原性阿尔法病毒会导致人类显著的肌肉骨疾病.
- 介导阿尔法病毒进入细胞的宿主因素尚不清楚.
研究的目的:
- 识别关节性阿尔法病毒进入细胞的重要宿主因素.
- 评估Mxra8作为对抗阿尔法病毒感染的潜在治疗点.
主要方法:
- 全基因组CRISPR-Cas9查以确定宿主进入因素.
- 哺乳动物细胞中Mxra8的基因编辑 (敲除和异位表达).
- 使用Mxra8-Fc融合蛋白和单克隆抗体进行体内结合测定和阻断感染的研究.
- 在小鼠模型中进行体内研究以评估治疗效果.
主要成果:
- Mxra8被确定为多种关节性阿尔法病毒的进入的关键媒介.
- Mxra8直接与病毒颗粒结合,并促进病毒的附着和内化.
- 阻断Mxra8功能显著降低了各种人类细胞类型和小鼠的病毒感染.
- 针对Mxra8的治疗干预降低了病毒载量,并减轻了体内疾病症状.
结论:
- Mxra8是关节性阿尔法病毒的关键宿主细胞受体.
- 针对Mxra8是一种有前途的治疗策略,用于对抗由奇孔尼亚病毒,罗斯河病毒,玛雅罗病毒和O'nyong nyong病毒引起的感染.
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