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Demyelinating and nondemyelinating strains of mouse hepatitis virus differ in their neural cell tropism
Jayasri Das Sarma1, Kathryn Iacono, Lilli Gard
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Jayasri.Das-Sarma@jefferson.edu
Abstract:
Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is a correlation between the differential localization of viral antigen in spinal cord gray matter and that in white matter during acute infection and the ability to induce demyelination later on. Viral antigen from demyelinating strains is detected initially in both gray and white matter, with subsequent localization to white matter of the spinal cord, whereas viral antigen localization of nondemyelinating strains is restricted mainly to gray matter. This observation suggests that the localization of viral antigen to white matter during the acute stage of infection is essential for the induction of chronic demyelination. Overall, these observations suggest that isogenic demyelinating and nondemyelinating strains of MHV, differing in the spike protein expressed, infect neurons and glial cells in different proportions and that differential tropism to a particular CNS cell type may play a significant role in mediating the onset and mechanisms of demyelination.
Insights
Mouse hepatitis virus (MHV) strains that cause demyelination target white matter in the spinal cord. This specific tropism, or cell targeting, is crucial for inducing chronic inflammatory demyelination similar to multiple sclerosis.
Area of Science:
- Neurovirology
- Immunology
- Pathology
Background:
- Mouse hepatitis virus (MHV) infection in mice can model aspects of multiple sclerosis, a human demyelinating disease.
- Previous research indicated that MHV strains differing in their spike gene exhibit varying neurovirulence and demyelinating potential.
Purpose of the Study:
- To investigate the role of central nervous system (CNS) cell tropism in MHV-induced demyelination.
- To determine if differences in neural cell tropism correlate with the demyelinating capacity of MHV strains.
Main Methods:
- Comparison of neural cell tropism between demyelinating and nondemyelinating MHV strains.
- Analysis of viral antigen localization in the spinal cord during acute infection.
- Correlation of viral antigen distribution with the induction of chronic demyelination.
Main Results:
- Isogenic MHV strains, differing in their spike gene, exhibit distinct patterns of infection in CNS cells.
- Viral antigen localization differs significantly between demyelinating and nondemyelinating strains.
- Demyelinating strains show initial antigen presence in both gray and white matter, with subsequent white matter accumulation, while nondemyelinating strains are primarily restricted to gray matter.
Conclusions:
- Differential tropism to specific CNS cell types, particularly white matter, is essential for MHV to induce chronic demyelination.
- The spike protein influences MHV tropism and subsequent demyelinating potential.
- Understanding MHV cell tropism provides insights into the mechanisms of demyelination relevant to multiple sclerosis.
