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FHL1是感染奇孔古尼亚病毒的主要宿主因子

Laurent Meertens¹, Mohamed Lamine Hafirassou², Thérèse Couderc³

¹INSERM U944, CNRS UMR 7212, Genomes & Cell Biology of Disease Unit, Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis, Paris, France. laurent.meertens@inserm.fr.

|September 27, 2019

概括

四个半个LIM域蛋白1 (FHL1) 对奇孔尼亚病毒 (CHIKV) 感染至关重要. 阻断FHL1可以抑制CHIKV,为这种蚊子传播的疾病提供新的治疗点.

科学领域:

病毒学
分子生物学
免疫学

背景情况:

奇孔古尼亚病毒 (CHIKV) 是一种重新出现的阿尔法病毒,导致显著的肌肉骨和关节疼痛.
了解对CHIKV感染至关重要的宿主因素对于开发有效疗法至关重要.

研究的目的:

确定人类细胞因子对于CHIKV的容许性和发病性至关重要.
研究四半LIM域蛋白1 (FHL1) 在CHIKV感染中的作用.

主要方法:

在人类和小鼠细胞中抑制FHL1表达的基因沉默.
用各种阿尔法病毒和黄病毒进行感染测试.
在FHL1和CHIKV nsP3之间进行蛋白相互作用研究.
在FHL1缺乏细胞和Fhl1失败小鼠中分析CHIKV感染.

主要成果:

除FHL1可以抑制CHIKV和o'nyong-nyong病毒的感染,但不能抑制其他alphavirus或flavivirus的感染.
在正常耐药细胞中促进CHIKV感染.
FHL1与CHIKV nsP3直接相互作用,对病毒RNA复制至关重要.
在Fhl1- knockout小鼠和FHL1- 缺乏患者衍生的细胞中,CHIKV感染无法检测.

结论:

FHL1是一个关键的宿主因子,可使CHIKV感染和发病.
CHIKV nsP3和FHL1之间的相互作用代表了抗CHIKV治疗开发的有希望的目标.

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