State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, PR China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, 361102, PR China.
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, PR China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, 361102, PR China.
Antiviral Res. 2024 Jan;221:105781. doi: 10.1016/j.antiviral.2023.105781. Epub 2023 Dec 12.
Coxsackievirus B6 (CVB6), a member of the human enterovirus family, is associated with severe diseases such as myocarditis in children. However, to date, only a limited number of CVB6 strains have been identified, and their characterization in animal models has been lacking. To address this gap, in this study, a neonatal murine model of CVB6 infection was established to compare the replication and virulence of three infectious-clone-derived CVB6 strains in vivo. The results showed that following challenge with a lethal dose of CVB6 strains, the neonatal mice rapidly exhibited a series of clinical signs, such as weight loss, limb paralysis, and death. For the two high-virulence CVB6 strains, histological examination revealed myocyte necrosis in skeletal and cardiac muscle, and immunohistochemistry confirmed the expression of CVB6 viral protein in these tissues. Real-time PCR assay also revealed higher viral loads in the skeletal and cardiac muscle than in other tissues at different time points post infection. Furthermore, the protective effect of passive immunization with antisera and a neutralizing monoclonal antibody against CVB6 infection was evaluated in the neonatal mouse model. This study should provide insights into the pathogenesis of CVB6 and facilitate further research in the development of vaccines and antivirals against CVBs.
柯萨奇病毒 B6（CVB6）是人类肠道病毒家族的一员，与儿童心肌炎等严重疾病有关。然而，迄今为止，仅鉴定出有限数量的 CVB6 毒株，并且在动物模型中对其特征的研究也有所欠缺。为了解决这一差距，本研究建立了 CVB6 感染的新生鼠模型，以比较三种传染性克隆衍生的 CVB6 株在体内的复制和毒力。结果表明，在接受致死剂量的 CVB6 株攻击后，新生鼠迅速表现出一系列临床症状，如体重减轻、四肢瘫痪和死亡。对于两种高毒力的 CVB6 株，组织学检查显示骨骼肌和心肌中的肌细胞坏死，免疫组织化学证实 CVB6 病毒蛋白在这些组织中的表达。实时 PCR 检测还显示，在感染后不同时间点，骨骼肌和心肌中的病毒载量均高于其他组织。此外，还评估了抗 CVB6 感染的抗血清和中和单克隆抗体的被动免疫对新生鼠模型的保护作用。本研究应为 CVB6 的发病机制提供深入了解，并有助于进一步研究针对 CVB 的疫苗和抗病毒药物的开发。
