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Nasoencephalopathy of mice infected intrananasally with a mouse hepatitis virus, JHM strain
Abstract:
A mouse hepatitis virus, strain JHM, grown on DBT cell culture was inoculated intranasally into ICR-SLC weanling mice, and histopathological lesions were studied in relation to viral growth. In the spleen virus titer reached a peak of 10(3) PFU/0.2G 48 H after inoculation, and later it decreased gradually. No virus was detected from the liver throughout the experiment, while some early inflammatory reactions appeared in the spleen and liver without any further development. At 48 h postinoculation there existed degeneration and necrosis in the nasal mucosa and submocosa. In the brain and spinal cord active viral growth was seen at 48 h postinfection or later. In the olfactory bulb mitral cells were also affected with accumulation of glial cells and some meningitis. At 72 to 96 h postinoculation, degeneration of neurons and glial cells were remarkable in the tructus olfactorius, cortex of lobus piriformis, septa pellucidum and commissura anterior accompanying meningitis. At 120 h postinfection, pyramidal cells in the hippocumpus were also degenerated and necrotized, and nodular proliferation and collapse of glial cells, small foci of demyelination and perivascular cuffing were seen in the interbrain. At 144 h postinoculation or later, the lesions developed through the whole brain including the pons and medulla oblongata as well as spinal cord. Brain virus titers showed 10(5) PFU/0.2g at 120 h and 10(4) PFU/0.2g at 144 h postinfection. In mice surviving at 168 hr after inoculation severe demyelinating lesions were observed despite of a decreased virus titer. These findings suggest that intranasally inoculated virus might invade the olfactory bulb through the tractus olfactorius and then produce necrotizing lesions, extending later towards the posterior parts of the central nervous system.
Insights
Intranasal inoculation of mouse hepatitis virus (MHV) strain JHM in mice causes progressive central nervous system demyelination. The virus spreads from the olfactory bulb to the brain and spinal cord, leading to severe lesions.
Area of Science:
- Neuroscience
- Virology
- Pathology
Background:
- Mouse hepatitis virus (MHV) strain JHM is a neurotropic pathogen.
- Understanding MHV pathogenesis is crucial for developing antiviral strategies.
- Previous studies have indicated MHV's potential to affect the central nervous system.
Purpose of the Study:
- To investigate the histopathological lesions and viral growth of MHV strain JHM after intranasal inoculation in mice.
- To elucidate the route of viral invasion and spread within the central nervous system.
- To correlate viral replication with observed neuropathological changes.
Main Methods:
- ICR-SLC weanling mice were inoculated intranasally with MHV strain JHM grown in DBT cell culture.
- Histopathological examination of tissues, including nasal mucosa, spleen, liver, brain, and spinal cord, was performed.
- Viral titers were quantified at various time points post-inoculation.
Main Results:
- Virus was detected in the spleen, peaking at 48 hours, but not in the liver.
- Nasal mucosa showed degeneration and necrosis by 48 hours post-inoculation.
- Active viral growth and neuropathology, including meningitis and neuronal/glial cell damage, were observed in the brain and spinal cord, progressing to widespread lesions by 144 hours.
- Severe demyelinating lesions were evident in surviving mice despite decreased viral titers.
Conclusions:
- Intranasal MHV strain JHM inoculation leads to neuroinvasion, likely via the olfactory bulb and tractus olfactorius.
- The virus causes necrotizing lesions that spread to posterior CNS regions, resulting in demyelination.
- The findings highlight the neurovirulence of MHV strain JHM and its potential to induce severe demyelinating disease.