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Acute and subacute demyelination induced by mouse hepatitis virus strain A59 in C3H mice
J L Woyciechowska1, B D Trapp, D H Patrick
1National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20205.
Abstract:
Mouse hepatitis virus (MHV, strain A-59), a coronavirus, induced acute and subacute demyelinating disease in the central nervous system of weanling C3H mice that were reported to be genetically resistant to MHV. Subtle clinical signs developed in greater than 90% of animals 5-7 days after intracerebral inoculation of 25 PFU, and foci of demyelination were detected from 1 to 4 weeks postinoculation (p.i.) by histopathology and immunolabeling with antibody directed against myelin basic protein. Infectious virus could be isolated only during the first 10 days p.i., but viral antigens persisted in the cytoplasm of oligodendrocytes in the demyelinating lesions for up to 4 weeks p.i. Serum antibody titers against MHV-A59 rose by 2 weeks p.i. and persisted at high levels for months. This infection of genetically "resistant" animals by a normally hepatotropic strain of MHV can serve as a highly reproducible model for the study of acute and subacute demyelination by a coronavirus.
Insights
Mouse hepatitis virus (MHV) causes demyelinating disease in genetically resistant mice. This reproducible coronavirus model aids in studying central nervous system demyelination.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Mouse hepatitis virus (MHV) is a coronavirus.
- Typically, C3H mice are genetically resistant to MHV.
- MHV usually causes hepatitis, not central nervous system disease.
Purpose of the Study:
- To investigate the potential of MHV (strain A-59) to induce demyelinating disease in genetically resistant mice.
- To establish a reproducible animal model for studying coronavirus-induced demyelination.
Main Methods:
- Intracerebral inoculation of weanling C3H mice with MHV (strain A-59).
- Monitoring for clinical signs of disease.
- Histopathological examination and immunolabeling for myelin basic protein to detect demyelination.
- Virus isolation and detection of viral antigens in the central nervous system.
- Measurement of serum antibody titers against MHV.
Main Results:
- Subtle clinical signs of neurological disease observed in over 90% of mice within 5-7 days post-inoculation.
- Demyelination foci detected between 1 and 4 weeks post-inoculation.
- Infectious virus isolated only within the first 10 days post-inoculation.
- Viral antigens persisted in oligodendrocytes for up to 4 weeks post-inoculation.
- High and persistent serum antibody titers against MHV developed by 2 weeks post-inoculation.
Conclusions:
- MHV (strain A-59) can induce acute and subacute demyelinating disease in genetically resistant C3H mice.
- The persistent presence of viral antigens in oligodendrocytes suggests a role in sustained demyelination.
- This model provides a valuable tool for studying the pathogenesis of coronavirus-induced demyelination.