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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Coxsackievirus-induced acute neonatal central nervous system disease model
Lulu Wang1, Changyuan Dong1, Dong-E Chen2
1Laboratory of Molecular Virus & Cancer, State Key Laboratory of Virology, Wuhan University School of BasicMedicine Wuhan 430071, China.
Insights
Researchers developed a new mouse model for Coxsackievirus B (CVB) central nervous system (CNS) disease by oral infection. This model effectively mimics natural infection, aiding research into CVB-induced pediatric CNS conditions and their sequelae.
Area of Science:
- Virology
- Neuroscience
- Pathology
Background:
- Coxsackievirus B (CVB) is a major cause of acute pediatric central nervous system (CNS) disease, often leading to severe long-term neurological deficits.
- Existing research models do not fully replicate natural CVB infection routes or the acute onset of CNS disease.
- A need exists for a stable, reproducible model to study CVB pathogenesis and develop effective interventions.
Purpose of the Study:
- To establish a novel acute neonatal mouse model of CVB-induced CNS disease that mimics natural infection.
- To characterize the pathological features and viral dissemination within the CNS.
- To develop a standardized method for quantitative pathology analysis.
Main Methods:
- Neonatal mice were orally infected with Coxsackievirus B to establish the disease model.
- Histopathological analysis of brain tissues (hippocampus and cortex) was performed.
- A quantitative pathology scoring system was developed and validated.
- Viral tracking across the blood-brain barrier was visualized in vivo.
- A novel CVB3/Macocy strain was isolated, sequenced, and characterized.
Main Results:
- The oral CVB infection model successfully induced acute CNS disease, characterized by significant lesions in the hippocampus and cortex.
- The model demonstrated stability and reproducibility, accurately reflecting natural infection dynamics.
- The study captured the in vivo process of CVB breaching the blood-brain barrier.
- A novel CVB3 variant (CVB3/Macocy) was identified, with its genomic structure and genotype elucidated.
- Specific genomic mutations were identified in the new strain that did not alter the severity of CNS damage.
Conclusions:
- The established neonatal mouse model provides an effective platform for studying CVB-induced CNS diseases.
- This model facilitates research into viral entry mechanisms and neuropathogenesis.
- The characterization of the CVB3/Macocy strain contributes to understanding viral diversity and evolution.
Abstract:
Coxsackievirus B (CVB) is a significant pathogen that causes pediatric central nervous system disease with acute syndromes commonly. The onset of its infection was abrupt, and after recovery there usually will be severe mental sequelae. The disease model for research was not established by the way of natural infection, although there are various investigations about the CVB-induced central nervous system (CNS) diseases. Thus, we have established an acute neonatal CNS disease mice model by CVB orally infecting. This model imitated the natural infection route and focuses the onset of CNS disease, inducing severe infection and lesion in the hippocampus and cortex regions, and the stability of the model was demonstrated. A pathology score system was developed for quantitative pathology analysis, which standardizes the CNS pathology analysis by statistics analysis. By this model, the track of CVB penetrating the blood brain barrier in vivo has been captured. One of the experimental strains CVB3/Macocy, as a new variant, was isolated, and its genomic RNA was cloned. According to its nucleotide sequence, we have characterized its genomic structure and defined its genotype. Based on the sequence, some mutations which do not change the CVB-induced CNS damage have been found. The model is an effective tool for studies on CVB-induced CNS diseases.
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