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.
Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Virol Sin. 2022 Aug;37(4):610-618. doi: 10.1016/j.virs.2022.06.007. Epub 2022 Jun 28.
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.
柯萨奇病毒 A10（CV-A10）是引起手足口病（HFMD）的病原体之一，也可引起人类多种疾病，包括肺炎和心肌炎。不同的人，特别是儿童，对感染的免疫反应可能不同。目前的 CV-A10 感染动物模型仅提供了对该病毒发病机制和作用的初步了解。CV-A10 在人类中的感染、复制和脱落特征尚不清楚。在本研究中，通过呼吸道或消化道途径感染恒河猴以模拟人类 HFMD。在急性感染（感染后 1-11 天）和恢复期（感染后 12-180 天）中研究了临床症状、病毒脱落、炎症反应和病理变化。所有急性感染的恒河猴均表现出明显的病毒血症和临床症状，与人类观察到的症状相似。在多个器官中观察到大量炎症性病理损伤，包括肺、心、肝和肾。在急性期间，所有恒河猴均显示出临床症状、病毒脱落、血清细胞因子正常化和血清中和抗体增加，而炎症因子导致一些动物在恢复期出现严重高血糖。此外，呼吸道和消化道感染的动物之间没有显著差异。总体而言，所有数据表明，恒河猴提供了第一个用于研究 CV-A10 病理生理学和评估潜在人类治疗方法的非人类灵长类动物模型。
