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Updated: Jun 1, 2026

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
A mouse muscle-adapted enterovirus 71 strain with increased virulence in mice
Wei Wang1, Jianying Duo, Jiangning Liu
1Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, No.5 Panjiayuan Nanli, Chaoyang Dist, Beijing 100021, PR China.
Abstract:
Enterovirus 71 (EV71) infections can usually cause epidemic hand, foot, and mouth disease (HFMD), and occasionally lead to aseptic meningitis, encephalitis, and polio-like illness. Skeletal muscles have been thought to be crucial for the pathogenesis of EV71-related diseases. However, little is known about the virulence of mouse muscle-adapted EV71. The EV71 0805 were subjected to four passages in the mouse muscle to generate a mouse-adapted EV71 strain of 0805a. In comparison with the parental EV71 0805, the mouse muscle-adapted EV71 0805a displayed stronger cytotoxicity against Rhabdomyosarcoma (RD) cells and more efficient replication in RD cells. Furthermore, infection with the EV71 0805a significantly inhibited the gain of body weight, accompanied by increased muscle virus load and multiple tissue distribution in the infected mouse. Histological examinations indicated that infection with the EV71 0805 did not cause obvious pathogenic lesions in mice, while infection with the muscle-adapted 0805a resulted in severe necrotizing myositis in the skeletal and cardio muscles, and intestinitis in mice on day 5 post infection. Further analysis revealed many mutations in different regions of the genome of mouse muscle-adapted virus. Collectively, these data demonstrated the mouse muscle-adapted EV71 0805a with increased virulence in mice.
Insights
Enterovirus 71 (EV71) adapted to mouse muscle shows increased virulence. This adapted strain (0805a) causes severe muscle damage and disease in mice, unlike the original strain.
Area of Science:
- Virology
- Pathogenesis
- Molecular Biology
Background:
- Enterovirus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and severe neurological conditions.
- Skeletal muscle involvement is implicated in EV71 pathogenesis, but the virulence of muscle-adapted strains is poorly understood.
Purpose of the Study:
- To investigate the virulence of a mouse muscle-adapted EV71 strain (0805a) compared to its parental strain (0805).
Main Methods:
- EV71 0805 was passaged four times in mouse muscle to create the adapted strain 0805a.
- Cytotoxicity and replication assays were performed on Rhabdomyosarcoma (RD) cells.
- In vivo studies involved infecting mice to assess weight gain, viral load, tissue distribution, and histopathology.
Main Results:
- The adapted EV71 0805a exhibited enhanced cytotoxicity and replication in RD cells compared to EV71 0805.
- In mice, EV71 0805a infection led to reduced weight gain, increased muscle viral load, and widespread tissue distribution.
- Histological analysis revealed severe necrotizing myositis and intestinitis in mice infected with EV71 0805a, whereas the parental strain caused no significant lesions.
Conclusions:
- Mouse muscle adaptation significantly increased EV71 virulence.
- The adapted strain EV71 0805a causes severe muscle pathology and systemic disease in mice, highlighting the role of muscle adaptation in viral pathogenesis.

