Related Experiment Videos
Olfactory neural pathway in mouse hepatitis virus nasoencephalitis
1Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510.
Abstract:
The mechanism of brain infection with mouse hepatitis virus-JHM was studied in BALB/cByJ mice following intranasal inoculation, and found to be a consequence of direct viral spread along olfactory nerves into olfactory bulbs of the brain. Infection was followed sequentially from nose to brain, using microscopy, immunohistochemistry and virus quantification. Lesions, antigen and virus were observed in the olfactory bulb and anterior brain as early as 2 days and posterior brain by 4 days after inoculation. Viral antigen extended through nasal mucosa into submucosa, then coursed along the olfactory nerve perineurium and fibers, through the cribriform plate into the olfactory bulbs. On days 4 and 7, viral antigen was found in the antero-ventral brain, along ventral meninges, olfactory tracts and anterior ramifications of the lateral ventricles. Virus was cleared from nose by 10 days and anterior brain by 20 days, but persisted in posterior brain for 20 days after inoculation. Mice also developed disseminated infection, with viremia and hepatitis. Infection of brain did not correlate with presence of viremia. In contrast to intranasally inoculated mice, orally-inoculated mice did not develop encephalitis, despite evidence of disseminated infection.
Insights
Mouse hepatitis virus-JHM infects the brain through direct spread along olfactory nerves. This study details the nose-to-brain viral pathway and clearance dynamics in mice.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Mouse hepatitis virus-JHM (MHV-JHM) is a neurotropic coronavirus.
- Understanding viral entry into the central nervous system (CNS) is crucial for developing treatments.
Purpose of the Study:
- To elucidate the mechanism of MHV-JHM brain infection following intranasal inoculation.
- To track the sequential spread of the virus from the nose to the brain.
Main Methods:
- BALB/cByJ mice were intranasally inoculated with MHV-JHM.
- Infection was monitored using microscopy, immunohistochemistry, and virus quantification.
- Viral spread was traced from the nasal cavity to the brain.
Main Results:
- MHV-JHM spread directly along olfactory nerves into the olfactory bulbs.
- Viral antigen and lesions appeared in the olfactory bulb and anterior brain within 2 days, and posterior brain by 4 days.
- Virus was cleared from the nose by 10 days and anterior brain by 20 days, but persisted in the posterior brain for 20 days.
Conclusions:
- Intranasal inoculation leads to direct MHV-JHM spread to the brain via the olfactory pathway.
- Brain infection did not correlate with viremia.
- Oral inoculation did not result in encephalitis, suggesting route-specific infection patterns.