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Role of macrophages during Theiler's virus infection
C P Rossi1, M Delcroix, I Huitinga
1Unité des Virus Lents, URA 1157 Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
Abstract:
Theiler's virus, a murine picornavirus, causes a persistent infection of the central nervous system with chronic inflammation and primary demyelination. We examined the nature of infected cells at different times postinoculation (p.i.) with a combined immunocytochemistry-in situ hybridization assay. The virus was found in the gray matter of the brain, mostly in neurons, during the first week p.i. During the following weeks, the virus was present in the spinal cord, first in the gray and white matter, then exclusively in the white matter. Approximately 10% of infected cells were astrocytes at any time during the study. Infected oligodendrocytes were first noticed on day 14 p.i. and amounted to approximately 6% of infected cells. The number of infected macrophages increased with time and reached a plateau by day 21 p.i., when at least 45% of infected cells were macrophages. The role of blood-borne macrophages during infection was studied by depleting them with mannosylated liposomes containing dichloromethylene diphosphonate. The virus did not persist in the majority of the mice treated with liposomes. These mice showed only minimal mononuclear cell infiltration and no demyelination.
Insights
Theiler's virus infects neurons, astrocytes, and macrophages in the central nervous system. Depleting macrophages prevents persistent Theiler's virus infection and demyelination.
Area of Science:
- Neurovirology
- Immunology
- Demyelinating Diseases
Background:
- Theiler's virus causes persistent central nervous system (CNS) infection, leading to chronic inflammation and demyelination.
- Identifying the specific cell types infected by the virus is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To characterize the cell types infected by Theiler's virus at different stages of persistent CNS infection.
- To investigate the role of macrophages in Theiler's virus persistence and demyelination.
Main Methods:
- Combined immunocytochemistry and in situ hybridization were used to identify infected cells in the CNS.
- Macrophage depletion was achieved using mannosylated liposomes containing dichloromethylene diphosphonate.
Main Results:
- Theiler's virus initially infected neurons in the gray matter, later spreading to white matter in the spinal cord.
- Infected cells included neurons, astrocytes (approx. 10%), oligodendrocytes (approx. 6% after day 14), and macrophages (increasing to approx. 45%).
- Depletion of blood-borne macrophages significantly reduced viral persistence and prevented demyelination.
Conclusions:
- Macrophages play a critical role in the persistence of Theiler's virus infection in the CNS.
- Targeting macrophages may be a therapeutic strategy to prevent Theiler's virus-induced demyelination.