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Nitric oxide synthase type II expression by different cell types in MHV-JHM encephalitis suggests distinct roles for
D M Grzybicki1, K B Kwack, S Perlman
1Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Abstract:
Intranasal inoculation with mouse hepatitis virus strain JHM (MHV-JHM) results in acute meningoencephalitis. We found NOS II mRNA expression in brains of acutely infected animals on days 5 through 7 after infection. In situ hybridization and immunohistochemistry demonstrated NOS II message and protein in infiltrating macrophages. Persistent infection with MHV-JHM results in chronic demyelinating encephalomyelitis. NOS II mRNA was detected in persistently infected spinal cords. In situ hybridization and immunohistochemistry showed expression of NOS II in astrocytes in and around demyelinated lesions. These results suggest the role of NO release in acute versus persistent infection with this virus, and its contribution to the resulting pathology, may be different.
Insights
Mouse hepatitis virus (MHV-JHM) infection causes brain inflammation. Nitric oxide synthase II (NOS II) is found in macrophages during acute infection and in astrocytes during chronic demyelinating disease.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Mouse hepatitis virus strain JHM (MHV-JHM) causes acute meningoencephalitis and chronic demyelinating encephalomyelitis.
- Nitric oxide synthase II (NOS II) is an enzyme implicated in inflammatory processes.
Purpose of the Study:
- To investigate the expression and localization of NOS II during acute and persistent MHV-JHM infections.
- To determine the potential role of NOS II in the distinct pathologies of acute versus chronic viral encephalitis.
Main Methods:
- Intranasal inoculation of mice with MHV-JHM.
- Detection of NOS II mRNA using in situ hybridization.
- Detection of NOS II protein using immunohistochemistry.
- Analysis of brain and spinal cord tissues at different time points post-infection.
Main Results:
- NOS II mRNA and protein were detected in infiltrating macrophages in the brains of acutely infected mice (days 5-7).
- NOS II mRNA was found in persistently infected spinal cords.
- NOS II expression was observed in astrocytes surrounding demyelinated lesions in chronic infection.
Conclusions:
- NOS II expression differs between acute and persistent MHV-JHM infections.
- Macrophages are the primary source of NOS II during acute viral meningoencephalitis.
- Astrocytes contribute to NOS II expression in chronic demyelinating lesions, suggesting distinct roles in viral pathogenesis.