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Ependymitis, leukoencephalitis, hydrocephalus, and thrombotic vasculitis following chronic infection by mouse
Abstract:
Mouse hepatitis virus 3 (MHV 3) is either avirulent (resistant mice), hepatotropic (susceptible mice), or neurotropic (semisusceptible mice), depending on the strain of mice infected. In semisusceptible mice, infection led first to a transient meningitis, ependymitis, and leukoencephalitis, followed by a permanent communicating hydrocephalus and, later on, to a chronic thrombotic vasculitis affecting meningeal and parenchymal vessels at the brain stem level. Small foci of ischemic necrosis related to vascular occlusions were seen in the dorsal brain stem. Cyclophosphamide treatment of semisusceptible mice significantly reduced the meningeal infiltrates but did not prevent the development of hydrocephalus and other neuropathologic changes. Identical lesions occurred in fully susceptible mice infected with a low dose of virus, but no neurologic disorder could be induced in genetically resistant mice even following immunosuppression or intracranial inoculation. The leukoencephalitis differed from the demyelinating lesions observed with MHV 4. Vascular lesions were of particular interest. More attention should be given to the possibility of virus induced chronic cerebral vasculitis in man.
Insights
Mouse hepatitis virus 3 (MHV 3) causes varied outcomes in mice. In susceptible strains, MHV 3 infection can lead to hydrocephalus and chronic cerebral vasculitis, highlighting potential human health risks.
Area of Science:
- Virology
- Neuropathology
- Immunology
Background:
- Mouse hepatitis virus 3 (MHV 3) exhibits strain-dependent virulence in mice, ranging from avirulent to hepatotropic and neurotropic.
- Infection in semisusceptible mice can result in transient neurological inflammation followed by chronic complications.
Purpose of the Study:
- To investigate the neuropathologic consequences of MHV 3 infection in different mouse strains.
- To explore the potential for virus-induced chronic cerebral vasculitis.
Main Methods:
- Infection of genetically resistant, susceptible, and semisusceptible mice with MHV 3.
- Administration of cyclophosphamide to assess its effect on neuropathology.
- Histopathological examination of brain tissues to identify lesions.
Main Results:
- Semisusceptible mice developed meningitis, hydrocephalus, and chronic thrombotic vasculitis affecting brain stem vessels.
- Vascular occlusions led to focal ischemic necrosis in the brain stem.
- Cyclophosphamide treatment reduced inflammation but did not prevent hydrocephalus or vasculitis.
- Susceptible mice showed similar lesions with low-dose infection; resistant mice remained unaffected.
Conclusions:
- MHV 3 infection can induce significant neuropathology, including hydrocephalus and chronic cerebral vasculitis, in susceptible mouse models.
- The study suggests a need to consider viral-induced chronic cerebral vasculitis as a potential human health concern.