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Updated: Jul 4, 2026
A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis
Kien Chai Ong1, Munisamy Badmanathan, Shamala Devi
1Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Abstract:
We describe a model of Enterovirus 71 encephalomyelitis in 2-week-old mice that shares many features with the human central nervous system (CNS) disease. Mice were infected via oral and parenteral routes with a murine-adapted virus strain originally from a fatal human case. The mice succumbed to infection after 2 to 5 days. Vacuolated and normal-appearing CNS neurons showed viral RNA and antigens and virions by in situ hybridization, immunohistochemistry, and electron microscopy; inflammation was minimal. The most numerous infected neurons were in anterior horns, motor trigeminal nuclei, and brainstem reticular formation; fewer neurons in the red nucleus, lateral cerebellar nucleus, other cranial nerve nuclei, motor cortex, hypothalamus, and thalamus were infected. Other CNS regions, dorsal root, and autonomic ganglia were spared. Intramuscular-inoculated mice killed 24 to 36 hours postinfection had viral RNA and antigens in ipsilateral lumbar anterior horn cells and adjacent axons. Upper cord motor neurons, brainstem, and contralateral motor cortex neurons were infected from 48-72 hours. Viral RNA and antigens were abundant in skeletal muscle and adjacent tissues but not in other organs. The distinct, stereotypic viral distribution in this model suggests that the virus enters the CNS via peripheral motor nerves after skeletal muscle infection, and spread within the CNS involves motor and other neural pathways. This model may be useful for further studies on pathogenesis and for testing therapies.
Insights
A new mouse model mimics human Enterovirus 71 encephalomyelitis, showing viral spread from muscle to the central nervous system (CNS). This model aids research into EV-A71 pathogenesis and potential therapies.
Area of Science:
- Virology
- Neuroscience
- Pathology
Background:
- Enterovirus 71 (EV-A71) causes severe neurological disease, including encephalomyelitis, particularly in children.
- Existing animal models do not fully recapitulate the human central nervous system (CNS) pathology of EV-A71 infection.
Purpose of the Study:
- To develop and characterize a novel mouse model of EV-A71 encephalomyelitis.
- To investigate the viral distribution and spread within the CNS and peripheral tissues in this model.
Main Methods:
- Infection of 2-week-old mice with a murine-adapted EV-A71 strain via oral and parenteral routes.
- Analysis of viral RNA, antigens, and virions in CNS and peripheral tissues using in situ hybridization, immunohistochemistry, and electron microscopy.
- Assessment of viral distribution and temporal progression of infection.
Main Results:
- Mice developed fatal encephalomyelitis within 2-5 days post-infection.
- Infected neurons were primarily located in the anterior horns, motor trigeminal nuclei, and brainstem reticular formation, with minimal inflammation.
- Viral RNA and antigens were detected in skeletal muscle and peripheral motor nerves, suggesting entry into the CNS via these pathways.
Conclusions:
- This mouse model accurately replicates key features of human EV-A71 encephalomyelitis.
- The model demonstrates a distinct viral tropism, entering the CNS via peripheral motor nerves and spreading through neural pathways.
- This model provides a valuable tool for studying EV-A71 pathogenesis and evaluating therapeutic interventions.
