. doi: 10.1016/j.virs.2024.02.001
Citation: Suqin Duan, Wei Zhang, Yongjie Li, Yanyan Li, Yuan Zhao, Weihua Jin, Quan Liu, Mingxue Li, Wenting Sun, Lixiong Chen, Hongjie Xu, Jie Tang, Jinghan Hou, Zijun Deng, Fengmei Yang, Shaohui Ma, Zhanlong He. Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey .VIROLOGICA SINICA, 2024, 39(2) : 290-300.  http://dx.doi.org/10.1016/j.virs.2024.02.001

柯萨奇病毒B3 HFMD的叙利亚仓鼠和恒河猴的动物模型

  • 柯萨奇病毒B3(CVB3)是引起手足口病(HFMD)的病原体,其临床表现从轻到重不等。然而传统的CVB3感染小鼠研究主要导致病毒性心肌炎和胰腺炎,无法复制HFMD症状。这限制了我们对于CVB3病毒-宿主相互作用的理解。尽管叙利亚仓鼠和恒河猴已被广泛用于评估许多肠道病毒,但尚未有关于CVB3的系统报道。在本研究中,我们首次测试了叙利亚仓鼠通过不同途径对CVB3感染的敏感性。我们的研究发现,无论是腹腔注射还是鼻滴,都有效地使CVB3感染叙利亚仓鼠,导致典型的HFMD症状、鼻咽部定植和急性严重病理性损伤。值得注意的是,鼻滴组导致了更长的排毒周期和更严重的病理性损伤。在后续研究中,通过鼻滴感染CVB3的恒河猴也表现出HFMD症状、排毒、血清抗体转换、病毒核酸和抗原以及特定器官的病理性损伤,如心脏。令人惊讶的是,心肌酶水平没有显著差异。并且临床表现与常见轻症感染相似。总之,本研究建立了CVB3重症叙利亚仓鼠和轻症恒河猴HFMD模型,为理解病原学、预试验预防与评估和暴露后干预奠定了基础。

Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

  • Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention.

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    Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

      Corresponding author: Fengmei Yang, yangfenmei@imbcams.com.cn
      Corresponding author: Shaohui Ma, shaohuima@imbcams.com.cn
      Corresponding author: Zhanlong He, hzl@imbcams.com.cn
    • Institute of Medical Biology, Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease, Kunming, 650118, China

    Abstract: Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention.

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