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Comparative study of mouse brains infected with Japanese encephalitis virus by intracerebral or intraperitoneal
T Hase1, D R Dubois, P L Summers
1Department of Ultrastructural Pathology, Walter Reed Army Institute of Research, Washington, DC 20307.
Abstract:
The brains of mice infected with Japanese encephalitis (JE) virus by intracerebral inoculation (IC), intraperitoneal inoculation with sham intracerebral inoculation (IP+sIC), and intraperitoneal inoculation (IP) were studied by light and electron microscopy. The mortality rates and mean survival days were 100% and 4.8 days for the IC group, 92% and 9.0 days for the IP+sIC group, and 58% and 13.4 days for the IP group. Accordingly, the brain samples of sick mice were examined by light and electron microscopy 4 days post-inoculation (p.i.) for the IC group, 7 days p.i. for the IP+sIC group and 12 days p.i. for the IP group. In light microscopy, the mouse brains in the IC group showed little inflammatory change with only mild generalized glial-cell proliferation and mononuclear cell infiltration. In electron microscopy, however, a majority of neurons in the brain were seen to be infected with virus that replicated exclusively in the neuronal secretory system, including rough endoplasmic reticulum (RER) and the Golgi apparatus. In contrast, light microscopic observation of the brains from the IP+sIC and the IP groups showed prominent inflammatory changes with leucocytic infiltration and perivascular cuffing. Neuronal degeneration and neuronophagia were also prominent. In electron microscopy, neurons were infected in the same manner as in the IC group, but showed more advanced degenerative changes with marked cytoplasmic rarefaction and frequent neuronal disintegration. Mononuclear cells were frequently found in direct contact with degenerating and disintegrating neurons. The results showed that (a) the basic process of JE virus replication in brain neurons was present in the three groups of mice, (b) in the peripherally inoculated mice the process was accompanied by inflammatory reaction with resultant neuronal destruction, and (c) breach in the blood-brain barrier at the time of peripheral viral inoculation played an important role in the viral invasion of the CNS.
Insights
Japanese encephalitis (JE) virus replicates in neurons regardless of inoculation route. Peripheral inoculation causes inflammation and neuronal destruction, highlighting the blood-brain barrier
Area of Science:
- Neurovirology
- Pathology
- Immunology
Background:
- Japanese encephalitis (JE) virus is a significant cause of viral encephalitis globally.
- Understanding JE virus pathogenesis in the central nervous system (CNS) is crucial for developing effective treatments.
- The role of the blood-brain barrier in JE virus CNS invasion requires further elucidation.
Purpose of the Study:
- To investigate the neuropathological effects of JE virus infection in mice via different inoculation routes.
- To compare viral replication, neuronal damage, and inflammatory responses in the mouse brain.
- To assess the significance of the blood-brain barrier breach in JE virus CNS entry.
Main Methods:
- Mice were inoculated with JE virus via intracerebral (IC) or intraperitoneal (IP) routes.
- Mortality rates and survival times were recorded.
- Brain tissues were examined using light and electron microscopy at specific time points post-inoculation.
Main Results:
- JE virus replicated in neurons via the secretory pathway in all inoculation groups.
- Intracerebral inoculation resulted in high mortality with minimal inflammation but significant neuronal infection.
- Peripheral inoculation led to prominent inflammation, neuronal degeneration, and neuronophagia, suggesting blood-brain barrier disruption facilitates CNS invasion.
Conclusions:
- JE virus replication occurs similarly in neurons irrespective of the inoculation route.
- Peripheral JE virus infection triggers inflammatory responses leading to severe neuronal damage.
- Blood-brain barrier integrity is critical for preventing JE virus entry into the CNS.