State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
Hubei Jiangxia Laboratory, Wuhan, Hubei 430200, China.
Sci Adv. 2023 Aug 2;9(31):eadg6856. doi: 10.1126/sciadv.adg6856.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus causing a high fatality rate of up to 30%. To date, the receptor mediating SFTSV entry remained uncharacterized, hindering the understanding of disease pathogenesis. Here, C-C motif chemokine receptor 2 (CCR2) was identified as a host receptor for SFTSV based on a genome-wide CRISPR-Cas9 screen. Knockout of CCR2 substantially reduced viral binding and infection. CCR2 enhanced SFTSV binding through direct binding to SFTSV glycoprotein N (Gn), which is mediated by its N-terminal extracellular domain. Depletion of CCR2 in C57BL/6J mouse model attenuated SFTSV replication and pathogenesis. The peripheral blood primary monocytes from elderly individuals or subjects with underlying diabetes mellitus showed higher CCR2 surface expression and supported stronger binding and replication of SFTSV. Together, these data indicate that CCR2 is a host entry receptor for SFTSV infection and a novel target for developing anti-SFTSV therapeutics.
严重发热伴血小板减少综合征病毒（SFTSV）是一种新兴的蜱传布尼亚病毒，其致死率高达 30%。迄今为止，介导 SFTSV 进入的受体尚未被阐明，这阻碍了对疾病发病机制的理解。在这里，基于全基因组 CRISPR-Cas9 筛选，发现 C-C 基序趋化因子受体 2（CCR2）是 SFTSV 的宿主受体。CCR2 的敲除显著减少了病毒的结合和感染。CCR2 通过直接与 SFTSV 糖蛋白 N（Gn）结合增强 SFTSV 结合，这是由其 N 端细胞外结构域介导的。在 C57BL/6J 小鼠模型中耗尽 CCR2 可减弱 SFTSV 的复制和发病机制。来自老年人或患有潜在糖尿病的个体的外周血原代单核细胞表面表达更高水平的 CCR2，并支持 SFTSV 的更强结合和复制。总之，这些数据表明 CCR2 是 SFTSV 感染的宿主进入受体，也是开发抗 SFTSV 治疗药物的新靶点。
