Pathogenic analysis of coxsackievirus A10 in rhesus macaques

Suqin Duan; Fengmei Yang; Yanyan Li; Yuan Zhao; Li Shi; Meng Qin; Quan Liu; Weihua Jin; Junbin Wang; Lixiong Chen; Wei Zhang; Yongjie Li; Ying Zhang; Jingjing Zhang; Shaohui Ma; Zhanlong He; Qihan Li

doi:10.1016/j.virs.2022.06.007

August 2022

Suqin Duan, Fengmei Yang, Yanyan Li, Yuan Zhao, Li Shi, Meng Qin, Quan Liu, Weihua Jin, Junbin Wang, Lixiong Chen, Wei Zhang, Yongjie Li, Ying Zhang, Jingjing Zhang, Shaohui Ma, Zhanlong He and Qihan Li. Pathogenic analysis of coxsackievirus A10 in rhesus macaques[J]. Virologica Sinica, 2022, 37(4): 610-618. doi: 10.1016/j.virs.2022.06.007

Citation: Suqin Duan, Fengmei Yang, Yanyan Li, Yuan Zhao, Li Shi, Meng Qin, Quan Liu, Weihua Jin, Junbin Wang, Lixiong Chen, Wei Zhang, Yongjie Li, Ying Zhang, Jingjing Zhang, Shaohui Ma, Zhanlong He, Qihan Li. Pathogenic analysis of coxsackievirus A10 in rhesus macaques .VIROLOGICA SINICA, 2022, 37(4) : 610-618. http://dx.doi.org/10.1016/j.virs.2022.06.007

柯萨奇A10病毒在恒河猴体内的致病性分析

段素琴 ^a ,
杨凤梅 ^a ,
李艳艳 ^a ,
赵远 ^a ,
史荔 ^a ,
秦蒙 ^b ,
刘权 ^a ,
靳伟华 ^a ,
王俊斌 ^a ,
陈丽雄 ^a ,
张伟 ^a ,
李泳洁 ^a ,
张莹 ^a ,
张晶晶 ^a ,
马绍辉 ^a,, ,
和占龙 ^a,, ,
李琦涵 ^a,,

a. 中国医学科学院北京协和医学院医学生物学研究所云南省重症传染病疫苗研究开发重点实验室昆明 650118;
b. 北京化工大学生命科学与技术学院北京 100029

通讯作者： 马绍辉, shaohuima@imbcams.com.cn; 和占龙, hzl@imbcams.com.cn; 李琦涵, liqihan@imbcams.com.cn
收稿日期： 2021-08-17
录用日期： 2022-06-22

摘要

柯萨奇病毒A10（CV-A10）是与手足口病（HFMD）相关的病原体之一，并且还会引起人类的多种疾病，包括肺炎和心肌炎。不同的人，尤其是幼儿，可能对感染有不同的免疫反应。目前的CV-A10感染动物模型仅提供了对该病毒发病机制和影响的初步了解。CV-A10在人类中感染、复制和脱落的特征仍然未知。在这项研究中，恒河猴通过呼吸或消化途径感染CV-A10，以模拟人类手足口病的发生。在急性感染（感染后1-11天）和恢复期（感染后12-180天），观察动物临床症状、病毒脱落、炎症反应和病理变化。急性感染期间，所有受感染的恒河猴均表现出明显的病毒血症和临床症状，与在人类中观察到的症状类似。并且，在包括肺、心脏、肝脏和肾脏在内的多个器官中观察到大量炎症性病理损害。在急性期，所有恒河猴都表现出临床症状、病毒排毒，血清细胞因子正常化、血清中和抗体增加，而炎症因子导致一些动物在恢复期出现严重的高血糖。此外，呼吸道或消化道感染动物之间没有显着差异。总体而言，所提供的所有数据表明，恒河猴提供了用于研究CV-A10病理生理学和评估潜在人类疗法的第一个非人类灵长类动物模型。
- 柯萨奇病毒A10
- , 手足口病
- , 非人灵长类动物模型
- , 恒河猴
- , 致病分析

Pathogenic analysis of coxsackievirus A10 in rhesus macaques

Suqin Duan ^a ,
Fengmei Yang ^a ,
Yanyan Li ^a ,
Yuan Zhao ^a ,
Li Shi ^a ,
Meng Qin ^b ,
Quan Liu ^a ,
Weihua Jin ^a ,
Junbin Wang ^a ,
Lixiong Chen ^a ,
Wei Zhang ^a ,
Yongjie Li ^a ,
Ying Zhang ^a ,
Jingjing Zhang ^a ,
Shaohui Ma ^a,, ,
Zhanlong He ^a,, ,
Qihan Li ^a,,

a Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease, Kunming, 650118, China;
b Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China

Corresponding author: Shaohui Ma, shaohuima@imbcams.com.cn Zhanlong He, hzl@imbcams.com.cn Qihan Li, liqihan@imbcams.com.cn
Received Date: 17 August 2021
Accepted Date: 22 June 2022

Abstract

Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1–11 day post infection) and recovery period (12–180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.
- Coxsackievirus A10 (CV-A10)
- , Hand, Foot and mouth disease (HFMD)
- , Non-human primate model
- , Rhesus macaque
- , Pathogenic analysis

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10.1016j.virs.2022.06.007-ESM.docx