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Published on: December 3, 2013
Restricted canine distemper virus infection of oligodendrocytes
A Zurbriggen1, M Yamawaki, M Vandevelde
1Department of Animal Neurology, University of Berne, Switzerland.
Background:
Canine distemper virus, a morbillivirus induces multifocal demyelination in the central nervous system. The acute demyelination correlates with virus replication in brain cells, especially astrocytes. Observations in vivo and in vitro demonstrated degeneration of oligodendrocytes, the myelin producing cells. However, the mechanism of oligodendroglial degeneration in distemper remained unexplained. Infection of the myelin producing cells, the most obvious explanation for the phenomenon of demyelination, could not be supported by extensive searches for viral particles or antigens in these cells neither in vivo nor in vitro.
Experimental Design:
In the present study, we combined in situ hybridization to visualize viral nucleic acid sequences with immunofluorescence for oligodendroglial antigens.
Results:
The nonradioactive in situ hybridization technique in combination with contrast enhanced video microscopy allowed us to unequivocally demonstrate the presence of canine distemper virus nucleic acid sequences in cultured oligodendrocytes. Many oligodendrocytes close to infected foci in the brain cell cultures were found to contain viral nucleic acid sequences. Only 1% of the viral nucleic acid sequences containing oligodendrocytes also contained viral antigen. Canine distemper virus replication in these cells is clearly restricted.
Conclusions:
Different possibilities why oligodendrocytes do not support a productive virus infection and mechanisms by which such a restricted infection leads to oligodendroglial degeneration and ensuing demyelination are discussed. While our results have advanced our understanding of the pathogenesis of acute demyelination in distemper, they may also offer a possible explanation for the chronic progressive or even relapsing course of the disease. A restricted infection of the oligodendrocytes may be the mechanism by which canine distemper virus persists in the central nervous system. Virus persistence is probably a key event in many chronic viral induced inflammatory demyelinating diseases.
Insights
Canine distemper virus nucleic acid was found in oligodendrocytes, the cells that produce myelin, but replication was restricted. This restricted infection may explain how the virus causes demyelination and persists in the central nervous system.
Area of Science:
- Neurovirology
- Central Nervous System Pathology
Background:
- Canine distemper virus (CDV) causes demyelination in the central nervous system (CNS).
- Oligodendroglial degeneration, crucial for demyelination, was observed but its mechanism remained unclear.
- Direct CDV infection of oligodendrocytes was not previously supported by evidence.
Purpose of the Study:
- To investigate the mechanism of oligodendroglial degeneration in canine distemper.
- To determine if canine distemper virus infects oligodendrocytes.
Main Methods:
- Combined in situ hybridization for viral nucleic acid with immunofluorescence for oligodendroglial antigens.
- Utilized contrast-enhanced video microscopy for visualization.
Main Results:
- Canine distemper virus nucleic acid sequences were unequivocally detected in cultured oligodendrocytes.
- Oligodendrocytes near infected foci contained viral nucleic acid, but viral antigen was present in only 1% of these cells, indicating restricted replication.
- Canine distemper virus replication within oligodendrocytes is significantly restricted.
Conclusions:
- Restricted canine distemper virus infection of oligodendrocytes is demonstrated.
- This restricted infection likely explains oligodendroglial degeneration and subsequent demyelination.
- Restricted viral infection may be a mechanism for CDV persistence in the CNS, potentially explaining chronic inflammatory demyelinating diseases.
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