Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.
Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.
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DOI：
10.3389/fmicb.2021.658093
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发表时间：
2021
影响因子：
5.2
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Ji W;Qin L;Tao L;Zhu P;Liang R;Zhou G;Chen S;Zhang W;Yang H;Duan G;Jin Y
柯萨奇病毒（CV） A2已成为手足口病（手足口病）病原体谱中的重要病原体。CVA2感染的症状一般较轻，但在某些人身上会迅速恶化，对儿童健康构成严重威胁。然而，与肠病毒71型在死亡病例中频繁检出相比，由于CVA2的临床病程为良性，因此对其感染的关注有限。在本研究中，我们从手足口病感染中鉴定出3株CVA2菌株，并使用细胞适应性CVA2菌株HN202009对5日龄BALB/c小鼠进行肌肉接种。这些小鼠出现了明显的神经系统症状，如共济失调、后肢麻痹和死亡。组织病理学检查显示神经吞噬、肺出血、肌纤维溶解、病毒性心肌炎。在多个器官和组织中检测到病毒复制，CVA2表现出强烈的肌肉组织趋向性。疾病的严重程度与炎症细胞因子的异常高水平有关，包括白细胞介素(IL)-6、IL-10、肿瘤坏死因子α和单核细胞趋化蛋白1，尽管阻断这些促炎细胞因子没有明显的保护作用。我们还测试了实验性甲醛灭活CVA2疫苗是否能在成年小鼠中诱导保护性免疫反应。免疫小鼠CVA2抗血清对CVA2感染有效。此外，CVA2灭活疫苗在新生小鼠体内也能成功产生免疫保护作用。我们的结果表明，新生小鼠模型可以作为研究CVA2感染和开发CVA2疫苗的有用工具。
Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children’s health. However, compared with enterovirus 71 detected frequently in fatal cases, limited attention has been paid to CVA2 infections because of its benign clinical course. In the present study, we identified three CVA2 strains from HFMD infections and used the cell-adapted CVA2 strain HN202009 to inoculate 5-day-old BALB/c mice intramuscularly. These mice developed remarkably neurological symptoms such as ataxia, hind-limb paralysis, and death. Histopathological determination showed neuronophagia, pulmonary hemorrhage, myofiberlysis and viral myocarditis. Viral replication was detected in multiple organs and tissues, and CVA2 exhibited strong tropism to muscle tissue. The severity of illness was associated with abnormally high levels of inflammatory cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor α, and monocyte chemotactic protein 1, although the blockade of these proinflammatory cytokines had no obvious protection. We also tested whether an experimental formaldehyde-inactivated CVA2 vaccine could induce protective immune response in adult mice. The CVA2 antisera from the vaccinated mice were effective against CVA2 infection. Moreover, the inactivated CVA2 vaccine could successfully generate immune protection in neonatal mice. Our results indicated that the neonatal mouse model could be a useful tool to study CVA2 infection and to develop CVA2 vaccines.
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DOI：
10.1038/nrrheum.2015.169
发表时间：
2016-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Kalliolias GD;Ivashkiv LB
通讯作者：
Ivashkiv LB
影响因子：
11.8
作者：
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通讯作者：
Wei S
影响因子：
14.9
作者：
Lefkowitz EJ;Dempsey DM;Hendrickson RC;Orton RJ;Siddell SG;Smith DB
通讯作者：
Smith DB
DOI：
10.1016/s1684-1182(10)60016-3
发表时间：
2010-04-01
影响因子：
7.4
作者：
Chen, Shih-Perng;Huang, Yhu-Chering;Lin, Tzou-Yien
通讯作者：
Lin, Tzou-Yien
影响因子：
8
作者：
Chen, Kow-Tong;Chang, Hsiao-Ling;Yang, Jyh-Yuan
通讯作者：
Yang, Jyh-Yuan