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Human polyomavirus JCV and expression of myelin genes
J Gordon1, G L Gallia, L Del Valle
1Neurovirology and Cancer Biology, Temple University, 1900 North 12th St., 015-96 Philadelphia, PA 19122, USA.
Abstract:
Myelin basic protein (MBP) is a major component of the myelin sheath of both the central and peripheral nervous systems. A number of neurological diseases in humans are associated with demyelination of the central and/or peripheral nervous systems, including multiple sclerosis and its variants such as acute disseminated encephalomyelitis (AD), acute hemorrhagic leukoencephalopathy, and idiopathic polyneuritis (Guilliame-Barre syndrome), as well as tropical spastic paraparesis (TSP), and progressive multifocal leukoencephalopathy (PML). Multiple sclerosis (MS) is perhaps the most common demyelinating disease and is one of great importance to the clinical neurologist. The underlying cause of the demyelination seen in multiple sclerosis patients is unknown. However, patients frequently have unusually high antibody titers to a number of common viruses, leading to speculation that viral infections may participate in the pathogenesis of MS. On the other hand, studies on maternal and paternal twins have suggested the involvement of genetic factors in the predisposition of an individual toward developing MS. PML, once a rare demyelinating disease of elderly patients with lymphoproliferative disorders, is now a much more common disease affecting patients of all ages due to the increasingly widespread use of immunosuppressive chemotherapy and the prevalence of AIDS. PML is the result of productive infection of oligodendrocytes, the myelin producing cells of the CNS, with the human polyomavirus, JCV. In this article, we have focused our attention on PML, and the role of JCV in disrupting myelin sheaths by affecting myelin basic gene expression, ultimately leading to demyelination.
Insights
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the human polyomavirus, JCV. This virus disrupts myelin sheaths by affecting myelin basic protein gene expression, leading to central nervous system damage.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Myelin basic protein (MBP) is crucial for the central and peripheral nervous systems.
- Demyelinating diseases like multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) impact myelin.
- PML is increasingly prevalent due to immunosuppression and AIDS, affecting all age groups.
Purpose of the Study:
- To investigate the role of the human polyomavirus, JCV, in the pathogenesis of PML.
- To understand how JCV disrupts myelin sheaths and affects myelin basic gene expression.
Main Methods:
- Focus on Progressive Multifocal Leukoencephalopathy (PML) as the primary demyelinating disease model.
- Analysis of the interaction between JCV and oligodendrocytes (myelin-producing cells).
- Examination of the impact of JCV on myelin basic protein gene expression.
Main Results:
- JCV infection of oligodendrocytes is the direct cause of PML.
- JCV disrupts myelin sheaths by altering myelin basic protein gene expression.
- This disruption leads to demyelination in the central nervous system.
Conclusions:
- JCV is the causative agent of PML, a significant demyelinating disease.
- Understanding JCV's mechanism of myelin disruption is key to developing treatments for PML.
- The study highlights the link between viral infections and neurological disorders.