病毒包膜糖蛋白向双特异性T细胞参与者保护小鼠免受致命的严重发烧和血栓塞缩症病毒感染

病毒包膜糖蛋白向双特异性T细胞参与者保护小鼠免受致命的严重发烧和血栓塞缩症病毒感染

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Xuefang Peng¹, Wei Wang², Yuexia Liang³

¹State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.

Cell reports. Medicine

|November 19, 2025

概括

严重发烧与血小板缺血综合征 (SFTS) 涉及T细胞功能障碍. 针对SFTSV糖蛋白的双特异性T细胞诱因 (BiTE) 抗体在治疗这种新出现的出血性发烧方面表现有前途.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
分子生物学分子生物学

背景情况:

严重发烧与血小板缺血综合征 (SFTS) 是一种新兴的病毒性出血性发烧,具有流行病潜力.
人与人之间的传播和高死亡率强调了迫切需要有效干预的必要性.
目前对SFTS病毒 (SFTSV) 感染的治疗选择有限.

研究的目的:

调查T细胞响应在SFTS病原发生中的作用.
开发一种针对SFTSV感染细胞的新型治疗策略.

主要方法:

单细胞RNA测序 (scRNA-seq) 和流细胞测量用于分析SFTS患者的T细胞状态.
用一种传染性小鼠模型来研究T细胞枯竭效应.
设计和测试了针对SFTSV包膜糖蛋白 (Gn) 的两种特异性T细胞吸引剂 (BiTE) 抗体.

主要成果:

SFTS患者表现出T细胞缺乏和功能障碍,特别是细胞毒性受损和CD4+T细胞耗尽,与致命结果相关.
在小鼠中CD4+和CD8+T细胞的枯竭增加了病毒病和死亡率.
针对病毒包膜糖蛋白的BiTE抗体成功地重定向T细胞以消除感染细胞,拯救小鼠免受致命的SFTSV感染.

结论:

T细胞损伤是SFTS致死性的关键因素.
针对Gn的BiTE代表了对SFTSV感染的有前途的治疗方法.
这项研究为开发针对SFTS的新型免疫疗法提供了基础.

关键词:

有关T细胞细胞毒性 T细胞耗尽的情况抗病毒药物抗病毒药物双特异性T细胞参与者.严重的发烧与血小板缺血综合征病毒.

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