A mouse-adapted CVA6 strain exhibits neurotropism and triggers systemic manifestations in a novel murine model.
A mouse-adapted CVA6 strain exhibits neurotropism and triggers systemic manifestations in a novel murine model.
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DOI：
10.1080/22221751.2022.2119166
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发表时间：
2022-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
--
作者：
CVA6是引起手足口病全球流行并伴有神经和全身并发症的肠病毒之一。研究CVA6的发病机制，评价其抗病毒作用和疫苗效果，需要合适的动物模型。在这项研究中，我们产生了一种小鼠适应CVA6菌株，通过口服途径成功感染了10日龄的ICR小鼠。所有感染小鼠均瘫痪并在11 dpi内死亡。对14个组织的病理变化和病毒载量的分析表明，CVA6引起的系统性损伤与接种途径相似。与ip途径不同，我们检测了存在病毒抗原的口腔和胃肠道病变。特异性抗cva6血清和灭活疫苗均能在小鼠体内产生免疫保护作用。同时，我们还成功地建立了10日龄小鼠经i.p.和i.m.途径感染CVA6的方法。感染后，小鼠出现明显的神经系统症状和全身表现，如消瘦、呼吸急促、四肢瘫痪、脱毛甚至死亡。通过免疫接种，病理检查显示病毒感染引起脑脊髓损伤，神经元减少，细胞凋亡，星形胶质细胞活化，中性粒细胞和单核细胞募集。在神经系统表现后，CVA6感染成为全身性感染，在多个器官中检测到高病毒载量，并伴有形态学改变和炎症。此外，通过FACS对脾脏细胞的分析表明，CVA6导致免疫系统激活，从而进一步导致全身炎症。综上所述，我们的CVA6小鼠模型为研究CVA6的发病机制和评估其抗病毒和疫苗效果提供了一个有用的工具。
CVA6 is one of Enteroviruses causing worldwide epidemics of HFMD with neurological and systemic complications. A suitable animal model is necessary for studying the pathogenesis of CVA6 and evaluating antiviral and vaccine efficacy. In this study, we generated a mouse-adapted CVA6 strain that successfully infected 10-day-old ICR mice via oral route. All infected mice were paralyzed and died within 11 dpi. Analysis of pathological changes and virus loads in fourteen tissues showed that CVA6 triggered systematic damage similar to i.p. inoculation route. Unlike i.p. route, we detected oral and gastrointestinal lesions with the presence of viral antigens. Both specific anti-CVA6 serum and inactivated vaccines successfully generated immune protection in mice. Meanwhile, we also established a successful infection of CVA6 via i.p. and i.m. route in 10-day-old mice. After infection, mice developed remarkably neurological signs and systemic manifestations such as emaciation, polypnea, quadriplegia, depilation and even death. Through i.p. inoculation, pathological examination showed brain and spinal cord damage caused by the virus infection with neuronal reduction, apoptosis, astrocyte activation, and recruitment of neutrophils and monocytes. Following neurological manifestation, the CVA6 infection became systemic, and high viral loads were detected in multiple organs along with morphological changes and inflammation. Moreover, analysis of spleen cells by FACS indicated that CVA6 led to immune system activation, which further contributed to systemic inflammation. Taken together, our novel murine model of CVA6 provides a useful tool for studying the pathogenesis and evaluating antiviral and vaccine efficacy.
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DOI：
10.3390/v13081588
发表时间：
2021-08-11
期刊：
Viruses
影响因子：
--
作者：
Ji W;Zhu P;Liang R;Zhang L;Zhang Y;Wang Y;Zhang W;Tao L;Chen S;Yang H;Jin Y;Duan G
通讯作者：
Duan G
影响因子：
5
作者：
Li, Ci-Xiu;Zhang, Bing;Lu, Yi-Yu
通讯作者：
Lu, Yi-Yu
影响因子：
4.2
作者：
Hu L;Maimaiti H;Zhou L;Gao J;Lu Y
通讯作者：
Lu Y
影响因子：
3.9
作者：
Ai Y;Zhang W;Wu J;Zhang J;Shen M;Yao S;Deng C;Li X;Wu D;Tian P;Cheng X;Zha H;Wu K
通讯作者：
Wu K
影响因子：
8.8
作者：
Blomqvist, Soile;Klemola, Paivi;Roivainen, Merja
通讯作者：
Roivainen, Merja