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Demyelination induced by murine coronavirus JHM infection of congenitally immunodeficient mice
J J Houtman1, H C Hinze, J O Fleming
1Department of Medical Microbiology, University of Wisconsin School of Medicine, USA.
Abstract:
Mouse hepatitis virus JHM (JHMV or MHV-4) induces demyelination in rodents and has been studied as a model for the human disease, multiple sclerosis (MS). As is proposed in MS, the mechanism of subacute demyelination induced by JHMV appears to be primarily immunopathological, since demyelination in JHMV-infected mice is abrogated by immunosuppressive doses of irradiation and restored by adoptive transfer of splenocytes. Thy-1+ cells play a critical role in transmitting disease to these recipient mice. To further characterize cells which may mediate JHMV-induced immunopathology, we inoculated congenitally immunodeficient mice with JHMV. By 12 days post-inoculation, both immunocompetent C57BL/6J controls and athymic nude C57BL/6 mice had severe paralysis and demyelination. In marked contrast, C57BL/6 mice with the severe combined immune deficiency (SCID) mutation had little or no paralysis or demyelination. Adoptive transfer of immune spleen cells from nude mice to infected SCID mice produced paralysis and demyelination. These findings suggest that a cell population present in immunocompetent C57BL/6J and nude mice but absent or non-functional in irradiated and SCID mice is essential for JHMV-induced demyelination. Identification of cells which mediate demyelination in this experimental system may have implications for our understanding of coronavirus pathogenesis and human demyelinating diseases.
Insights
Mouse hepatitis virus (MHV) causes demyelination in mice, a model for multiple sclerosis (MS). Immune cells are essential for this process, as SCID mice lacking them show no disease.
Area of Science:
- Neuroimmunology
- Virology
- Pathogenesis
Background:
- Mouse hepatitis virus JHM (JHMV) serves as a model for multiple sclerosis (MS) due to its demyelinating effects in rodents.
- The demyelination induced by JHMV is primarily immunopathological, as evidenced by its abrogation through immunosuppression and restoration via adoptive splenocyte transfer.
- Thy-1+ cells are implicated in disease transmission in JHMV-infected mice.
Purpose of the Study:
- To characterize the specific immune cells mediating JHMV-induced immunopathology and demyelination.
- To investigate the role of immune cell populations in the pathogenesis of JHMV infection using immunodeficient mouse models.
Main Methods:
- Inoculation of JHMV in congenitally immunodeficient mice, including athymic nude and severe combined immune deficiency (SCID) C57BL/6 mice.
- Comparison of disease progression (paralysis and demyelination) between immunocompetent controls and immunodeficient models.
- Adoptive transfer of immune spleen cells from nude mice to infected SCID mice to assess disease restoration.
Main Results:
- Both immunocompetent C57BL/6J and athymic nude mice exhibited severe paralysis and demyelination by 12 days post-inoculation with JHMV.
- In stark contrast, SCID mice infected with JHMV showed minimal to no paralysis or demyelination.
- Adoptive transfer of immune spleen cells into infected SCID mice successfully induced paralysis and demyelination, confirming the requirement for specific immune cells.
Conclusions:
- A specific immune cell population, present in immunocompetent and nude mice but absent or non-functional in SCID mice, is essential for JHMV-induced demyelination.
- These findings highlight the critical role of adaptive immunity in the pathogenesis of JHMV-induced demyelination.
- Identifying these mediating cells could advance understanding of coronavirus pathogenesis and human demyelinating diseases like MS.