A neonatal mouse model of coxsackievirus A10 infection for anti-viral evaluation
A neonatal mouse model of coxsackievirus A10 infection for anti-viral evaluation
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用于抗病毒评价的柯萨奇病毒 A10 感染新生小鼠模型
DOI：
10.1016/j.antiviral.2017.06.008
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发表时间：
2017-08-01
影响因子：
7.6
通讯作者：
Xia, Ningshao
中科院分区：
文献类型：
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作者：
Li, Shuxuan;Zhao, Huan;Xia, Ningshao
流行病学资料显示，柯萨奇病毒A10（CVA 10）已成为手足口病（HFMD）的主要病原体之一，近年来常与其他肠道病毒共同传播，给手足口病的防控带来挑战。虽然大多数与CVA 10相关的手足口病病例症状轻微，但也可能出现严重的表现，甚至死亡。然而，针对CVA 10感染的发病机制的研究以及药物和疫苗的开发仍远未完成。在这项研究中，我们建立了一个新生小鼠模型的抗病毒评价和特点的病理学CVA 10感染。为了建立小鼠模型，使用近交系和远交系小鼠品系来比较它们对CVA 10感染的敏感性;然后，选择1日龄BALB/c小鼠并腹腔内接种CVA 10临床品系CVA 10-FJ-01。在CVA 10感染的小鼠中观察到临床症状，如消瘦、后肢瘫痪甚至死亡。病理学检查和免疫组织化学染色显示，CVA 10感染小鼠出现严重的肌坏死和炎性细胞浸润，表明CVA 10对肌肉组织具有较强的嗜性。实时荧光定量PCR检测结果显示，CVA 10感染小鼠后不同时间点，血液和肌肉中的病毒载量均高于其他器官/组织中的病毒载量，提示CVA 10对小鼠肌肉有较强的嗜性，病毒血症扩散可能也是导致CVA 10感染小鼠死亡的原因之一。此外，为了评价CVA 10感染的新生小鼠模型，用福尔马林灭活的CVA 10免疫雌性小鼠，然后在第三次免疫后允许交配。结果表明，母源抗体对CVA 10感染小鼠具有保护作用。综上所述，结果表明新生小鼠模型是评价CVA 10疫苗和抗病毒试剂保护作用的有用工具。(C)2017爱思唯尔B. V.保留所有权利。
Epidemiological data indicate that coxsackievirus A10 (CVA10) has become one of the main causative agents of hand, foot and mouth disease (HFMD) and in recent years has often been found to co-circulate with other enteroviruses, which poses a challenge for the prevention and control of HFMD. Although most CVA10-associated HFMD cases present mild symptoms, severe manifestations and even death can also occur. However, the study of the pathogenesis and the development of drugs and vaccines for CVA10 infection are still far from complete. In this study, we established a neonatal mouse model for anti-viral evaluation and characterized the pathology of CVA10 infection. To develop the mouse model, both inbred and outbred mouse strains were used to compare their sensitivity to CVA10 infection; then, one-day-old BALB/c mice were selected and inoculated intraperitoneally with a CVA10 clinical strain, CVA10-FJ-01. Clinical symptoms, such as wasting, hind-limb paralysis and even death were observed in the CVA10-infected mice. Moreover, pathological examination and immunohistochemistry staining showed that severe myonecrosis with inflammatory infiltration was observed in CVA10-infected mice, indicating that CVA10 exhibited strong tropism to muscle tissue. Using real-time PCR, we also found that the viral load in the blood and muscle was higher than that in other organs/tissues at different time points post infection, suggesting that CVA10 had a strong tropism to mice muscle and that viremic spread may also contribute to the death of the CVA10-infected mice. Additionally, to evaluate the neonatal mouse model of CVA10 infection, female mice were immunized with formalin-inactivated CVA10 and then allowed to mate after the third immunization. The results showed that maternal antibodies could protect mice against CVA10 infection. In summary, the results demonstrated that the neonatal mice model was a useful tool for evaluating the protective effects of CVA10 vaccines and anti-viral reagents. (C) 2017 Elsevier B.V. All rights reserved.