Severe enterovirus A71 infection is associated with dysfunction of T cell immune response and alleviated by Astragaloside A

Chong Wang; Muhan Huang; Bingyu Guo; Xi Zhou; Zongqiang Cui; Yi Xu; Yujie Ren

doi:10.1016/j.virs.2025.05.010

June 2025

. doi: 10.1016/j.virs.2025.05.010

Citation: Chong Wang, Muhan Huang, Bingyu Guo, Xi Zhou, Zongqiang Cui, Yi Xu, Yujie Ren. Severe enterovirus A71 infection is associated with dysfunction of T cell immune response and alleviated by Astragaloside A .VIROLOGICA SINICA, 2025, 40(3) : 451-461. http://dx.doi.org/10.1016/j.virs.2025.05.010

与T细胞免疫功能障碍相关的肠道病毒A71重症感染可被黄芪甲苷缓解

王冲 ^a ,
黄霂晗 ^a ,
郭冰玉 ^a ,
周溪 ^a,b ,
崔宗强 ^a,b,, ,
徐翼 ^c,, ,
任玉洁 ^a,b,,

a 中国科学院生物安全大科学中心, 中国科学院武汉病毒研究所, 病毒学国家重点实验室;
b 中国科学院大学;
c 广州医科大学附属妇女儿童医疗中心传染病科

通讯作者： 崔宗强, czq@wh.iov.cn; 徐翼, xuyi70@163.com; 任玉洁, renyujie@wh.iov.cn
收稿日期： 2025-01-25
录用日期： 2025-05-26

摘要

肠道病毒A71（EV-A71）是导致重症手足口病（HFMD）的主要病原体。手足口病是一种主要影响儿童的传染病，临床患儿通常表现出严重的疾病进展，而感染的成人表现为轻症或无症状，其致病机制尚未完全明确，这阻碍了针对该疾病有效疗法的开发。本研究利用新生小鼠的EV-A71感染模型，发现T细胞的发育不全与EV-A71感染的严重程度密切相关，且EV-A71感染显著损害了T细胞免疫功能。结合T细胞缺失小鼠对EV-A71感染高度易感的数据，表明T细胞免疫功能障碍是导致EV71感染致病的关键因素。为了进一步评估T细胞免疫与手足口病之间的关系，本研究分析了145名经确诊的EV-A71感染儿童的临床数据，发现T细胞免疫反应受损与患儿的严重程度密切相关。此外，本研究发现用黄芪甲苷（一种来自中药黄芪的皂苷）治疗EV-A71感染新生小鼠，在T细胞依赖的方式下显示出对EV-A71感染的体内治疗效果。综上所述，本研究揭示了T细胞免疫与EV-A71感染致病的关系，为T细胞对手足口病发病进程的生理影响提供了新的见解，并发现了一种具有前景的针对EV-A71感染的免疫治疗策略。
- 肠道病毒A71
- , T细胞免疫
- , 手足口病
- , 黄芪甲苷
- , 免疫治疗策略

Severe enterovirus A71 infection is associated with dysfunction of T cell immune response and alleviated by Astragaloside A

Chong Wang ^a ,
Muhan Huang ^a ,
Bingyu Guo ^a ,
Xi Zhou ^a,b ,
Zongqiang Cui ^a,b,, ,
Yi Xu ^c,, ,
Yujie Ren ^a,b,,

a. State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China;
b. University of Chinese Academy of Sciences, Beijing 100049, China;
c. Department of Infectious Disease, Women and Children's Medical Center, Affiliated to Guangzhou Medical University, Guangzhou 510623, China

Corresponding author: Zongqiang Cui, czq@wh.iov.cn Yi Xu, xuyi70@163.com Yujie Ren, renyujie@wh.iov.cn
Received Date: 25 January 2025
Accepted Date: 26 May 2025

Abstract

Enterovirus A71 (EV-A71) is the major causative pathogen for severe hand-foot-mouth disease (HFMD), a predominantly childhood-associated communicable disease. The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized, which hinders the development of effective therapy against this disease. Herein, using the newborn mouse model of EV-A71 infection, we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection, and EV-A71 infection dramatically impaired T-cell immune response. Moreover, the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection, as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection. To further assess the relationship between T-cell immunity and HFMD, we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children. Furthermore, we found that the treatment of newborn mice with Astragaloside A, a saponin from the medicinal herb Astragalus membranaceus, showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner. In conclusion, these findings uncover the interaction between EV-A71 infection and T-cell immunity, provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD, and find a promising immunotherapeutic strategy to treat this viral disease.
- Enterovirus A71 (EV-A71)
- , T-cell immunity
- , hand-foot-and-mouth disease (HFMD)
- , Astragaloside A
- , Immunotherapeutic strategy

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Electronic Supplementary Material

10.1016j.virs.2025.05.010-ESM.docx