Development of A Neonatal Mouse Model for Coxsackievirus B1 Antiviral Evaluation.
Development of A Neonatal Mouse Model for Coxsackievirus B1 Antiviral Evaluation.
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用于柯萨奇病毒 B1 抗病毒评估的新生小鼠模型的开发
DOI：
10.1007/s12250-021-00444-1
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发表时间：
2021-12
影响因子：
5.5
通讯作者：
Xia N
中科院分区：
文献类型：
--
作者：
Yin Z;Wu Y;Zhu R;Xu L;Lin Y;Yang H;Fu W;Huang Q;Zhang D;Wang J;Wang W;Wang Y;Cheng T;Xia N
柯萨奇病毒B1 （CVB1）是人类严重传染病的主要病原体，据报道与无菌性脑膜炎、心肌炎的爆发和1型糖尿病（T1DM）等慢性疾病的发展有关。目前还没有批准的疫苗或有效的抗病毒疗法来治疗CBV1感染。用于评估抗病毒药物和疫苗效果的动物模型仍然有限。在本研究中，我们利用临床分离的CVB1菌株建立新生小鼠CVB1模型，以表征病毒感染的病理表现，促进CVB1疫苗和抗病毒药物的开发。1日龄BALB/c小鼠腹腔注射CVB1易感。低剂量CVB1攻击小鼠[10中位组织培养感染剂量（TCID50）]表现出一系列临床症状，如不活动、消瘦、四肢无力、毛发稀疏、驼背甚至死亡。病理检查和组织病毒载量分析显示，心脏、脊髓、肢体肌肉和肾脏均检测到CVB1阳性信号，无病理损害。特别是CVB1向胰腺有强烈的趋向性，引起严重的细胞坏死伴炎症浸润，并通过病毒血症传播。值得注意的是，从CVB1疫苗接种小鼠中获得的单克隆抗体（mAb） 6H5和抗血清可以有效地保护小鼠免受CVB1感染。综上所述，建立的新生小鼠模型是评估CVB1抗病毒试剂和疫苗疗效的有效工具。在线版本包含补充材料，下载地址为10.1007/s12250-021-00444-1。
Coxsackievirus B1 (CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus (T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose (TCID50)] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning, hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody (mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines. The online version contains supplementary material available at 10.1007/s12250-021-00444-1.
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