CCR2是严重发烧与血小板缩小综合征病毒的宿主进入受体
Leike Zhang1,2, Xuefang Peng3, Qingxing Wang1
1State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
Science advances
|August 2, 2023
概括
鉴定出C-C动机化学因子受体2 (CCR2) 是严重发烧与血栓塞维症综合征病毒 (SFTSV) 的宿主受体. 这一发现为开发治疗这种危险的传播疾病提供了一个新的目标.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 严重发烧与血小板缩小综合征病毒 (SFTSV) 是一种新兴的传播病原体,死亡率高.
- 宿主细胞进入机制和SFTSV的受体在很大程度上没有表征,限制了治疗的发展.
研究的目的:
- 为了识别介导SFTSV输入的宿主细胞受体.
- 阐明SFTSV与受体相互作用的机制.
- 探索已识别的受体在SFTSV病原和潜在的治疗向中的作用.
主要方法:
- 全基因组的CRISPR-Cas9查,以确定涉及SFTSV入境的宿主因素.
- 病毒结合测定和感染研究在具有或没有识别的受体的细胞系中.
- 蛋白质与蛋白质相互作用研究,绘制SFTSV与受体之间的结合接口.
- 使用C57BL/6J小鼠模型进行体内研究,以评估受体在SFTSV病变发生过程中的作用.
- 分析不同年龄组和患有并发症的个人初级人类单细胞中的受体表达.
主要成果:
- 鉴定出C-C动机化学因子受体2 (CCR2) 是SFTSV的功能性宿主受体.
- CCR2淘汰赛显著降低了SFTSV结合和病毒感染.
- CCR2通过其N端外细胞域直接与SFTSV糖蛋白Gn结合.
- 在小鼠中,CCR2的枯竭减弱了SFTSV的复制和疾病进展.
- 老年人和患有糖尿病的人在单细胞上表现出较高的CCR2表达,与增强的SFTSV结合和复制相关.
结论:
- CCR2 作为 SFTSV 的关键宿主进入受体.
- CCR2和SFTSV Gn之间的相互作用对于病毒进入至关重要.
- CCR2代表了对抗SFTSV感染的有希望的新型治疗标.
- 年龄和糖尿病可能通过CCR2表达水平影响SFTSV的易感性.
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