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Development of A Neonatal Mouse Model for Coxsackievirus B1 Antiviral Evaluation

  • RESEARCH ARTICLE
  • Published:
Virologica Sinica

Abstract

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.

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Acknowledgements

This research was supported by grants from the National Natural Science Foundation of China (No. 82072282 and 81801646), the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402-002-003) and the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2018ZX09711003-005-003). The sponsors had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Zhichao Yin and Yuanyuan Wu contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, China

    Zhichao Yin, Yuanyuan Wu, Rui Zhu, Longfa Xu, Yu Lin, Hongwei Yang, Wenkun Fu, Qiongzi Huang, Dongqing Zhang, Jue Wang, Wei Wang, Yingbin Wang, Tong Cheng & Ningshao Xia

Authors
  1. Zhichao Yin
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  2. Yuanyuan Wu
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  5. Yu Lin
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Contributions

NX, TC and YW conceived the experiments. ZY, RZ and LX wrote the manuscript. ZY and YW performed the majority of the laboratory work. YL and HY prepared of plasmids. WF, QH and DZ checked and finalized the manuscript. JW and WW prepared Coxsackievirus B1 for this study. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yingbin Wang or Tong Cheng.

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Conflict of interest

The authors declare that they have no conflict of interests.

Animal and Human Rights Statement

All of the animal experiments in this study were approved by the Institutional Animal Care and Use Committee at Xiamen University and conducted in accordance with animal ethics guidelines and approved protocols.

Supplementary Information

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Supplementary Fig. 1

CVB1 Conn-5 strain infection in mice resulted in dose-dependent mortality. One-day-old BALB/c mice were inoculated i.p. with CVB1 Conn-5 strain at a dose ranging from 100 to 102 TCID50/ mouse (10-fold serially diluted). The control mice were mock-infected with an equal volume of medium via the same route. CVB1, Coxsackievirus B1; TCID50, median tissue culture infective dose; i.p., intraperitoneally. (PDF 204 KB)

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Yin, Z., Wu, Y., Zhu, R. et al. Development of A Neonatal Mouse Model for Coxsackievirus B1 Antiviral Evaluation. Virol. Sin. 36, 1575–1584 (2021). https://doi.org/10.1007/s12250-021-00444-1

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  • DOI: https://doi.org/10.1007/s12250-021-00444-1

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