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Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS
1Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
JCV infects oligodendrocytes and, to a lesser extent, astrocytes in the brain and spinal cord and causes the demyelinating disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. The possibility exists that this opportunistic infection reactivates from a latent state in the brain. It is proposed that the pathogenetic immune response in a multiple sclerosis (MS) brain may be directed predominantly toward antigens of a DNA virus, such as JCV, which is latent in glial cells. The target antigens could be synthesized only during transient viral reactivation or could persist, thus explaining the two basic patterns of neurological symptoms in MS. It is further proposed that the viral genome as a minichromosome becomes focally distributed in glial cells following vertical passage in dividing progenitor cells after infection early in life. The concept that the host response to a single agent can evoke two distinct pathologies (PML and MS) derives from a chronic mycobacterial infection of peripheral nerves-leprosy.
Insights
John Cunningham virus (JCV) may cause both progressive multifocal leukoencephalopathy (PML) and multiple sclerosis (MS). This theory suggests latent JCV reactivation triggers distinct immune responses, explaining diverse neurological symptoms.
Area of Science:
- Neurovirology
- Immunology
- Neuropathology
Background:
- John Cunningham virus (JCV) is a human polyomavirus that infects glial cells, including oligodendrocytes and astrocytes, in the central nervous system.
- JCV infection in immunocompromised individuals can lead to progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease.
- The hypothesis proposes that JCV may also play a role in the pathogenesis of multiple sclerosis (MS).
Purpose of the Study:
- To propose a unifying hypothesis for the distinct neurological pathologies of PML and MS.
- To suggest that the immune response in MS may be directed against JCV antigens.
- To explain the variable clinical presentations of MS based on JCV reactivation patterns.
Main Methods:
- This study is theoretical, proposing a pathogenetic model based on existing knowledge of JCV and MS.
- It posits that JCV latency and reactivation in glial cells are key factors.
- The model considers the distribution of the viral genome within glial cells.
Main Results:
- The proposed model suggests that transient or persistent JCV antigen synthesis during reactivation could explain the diverse neurological symptoms observed in MS.
- It offers a potential explanation for how a single infectious agent, JCV, could be implicated in two distinct diseases: PML and MS.
- The concept draws parallels with leprosy, where a single pathogen elicits varied host responses.
Conclusions:
- JCV is a potential etiological factor in both PML and MS.
- The immune response to latent JCV reactivation in the brain may underlie the pathogenesis of MS.
- This hypothesis provides a framework for understanding the dual pathology of PML and MS stemming from a single viral infection.