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Distribution of papovavirus, myelin-associated glycoprotein, and myelin basic protein in progressive multifocal
Abstract:
To study how viruses interact with oligodendroglia and produce demyelination, we immunostained paraffin and epon sections of lesions from patients with progressive multifocal leukoencephalopathy (PML) with antisera to papovaviruses, oligodendroglial myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) according to the peroxidase-antiperoxidase method. In paraffin sections from a rapidly progressive case of PML, hyperimmune JC virus antiserum stained single oligodendroglia which were located in white matter that appeared normal histologically and stained normally with MAG and MBP antisera. In zones surrounding areas of demyelination, virus containing oligodendroglia were most numerous and MAG staining of periaxonal regions was decreased, but there was little change in MBP staining. In demyelinated regions, both MAG and MBP staining were severely altered; also there was much less JC virus staining. In tissue from three other chronic cases, viral antiserum stained fewer oligodendrocytes and the differences in MAG and MBP staining were much less striking. In epon sections from two biopsies of central nervous system tissue, we studied the electron microscopic appearance of oligodendroglia that also had been stained by JC virus antiserum. Virions were present in all nuclei and in some cytoplasmic regions. The results suggest that changes in MAG distribution are useful indicators of early oligodendroglial abnormalities which can cause myelin breakdown.
Insights
JC virus infection of oligodendroglia causes demyelination in progressive multifocal leukoencephalopathy (PML). Early changes in myelin-associated glycoprotein (MAG) indicate oligodendroglial abnormalities and myelin breakdown.
Area of Science:
- Neurovirology
- Neuropathology
- Cell Biology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by JC virus.
- Oligodendroglia are glial cells responsible for producing myelin in the central nervous system.
- Understanding the interaction between JC virus and oligodendroglia is crucial for elucidating PML pathogenesis.
Purpose of the Study:
- To investigate the interaction between JC virus and oligodendroglia in PML lesions.
- To determine the temporal relationship between viral infection, oligodendroglial changes, and demyelination.
- To identify early indicators of oligodendroglial dysfunction in PML.
Main Methods:
- Immunohistochemistry using antisera against JC virus, myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) on paraffin-embedded PML lesions.
- Electron microscopy of JC virus-infected oligodendroglia in epon-embedded tissue.
- Peroxidase-antiperoxidase staining method.
Main Results:
- JC virus was detected in oligodendroglia in both normal-appearing white matter and demyelinated areas.
- Decreased MAG staining was observed in the periaxonal regions surrounding demyelinated areas, preceding significant MBP alterations.
- JC virus staining was less prominent in severely demyelinated regions.
- Electron microscopy confirmed the presence of JC virus virions within the nuclei and cytoplasm of oligodendroglia.
Conclusions:
- JC virus infects oligodendroglia, leading to progressive demyelination in PML.
- Alterations in MAG distribution serve as early indicators of oligodendroglial abnormalities.
- These early changes in MAG are associated with subsequent myelin breakdown.