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Reappraisal of progressive multifocal leukoencephalopathy due to simian virus 40
G L Stoner1, C F Ryschkewitsch
1Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. stoner@helix.nih.gov
Abstract:
Several cases of progressive multifocal leukoencephalopathy (PML) have been associated with simian virus 40 (SV40), rather than with JC virus (JCV), the polyomavirus originally isolated from PML tissue. PML has, therefore, been defined as a demyelinating syndrome with possible multiple viral etiologies. Tissues from three of the cases thought to be associated with SV40 were available for reexamination. Monoclonal antibodies specific for SV40 capsid antigen VPI, virus-specific biotinylated DNA probes for in situ hybridization, and virus-specific primers in the polymerase chain reaction (PCR) were used. Macaque PML brain served as a positive control tissue for SV40 brain infection. Monoclonal antibodies to SV40 VPI failed to recognize viral antigen in lesions from all three human PML cases. The biotinylated DNA probe, which reacted with SV40 in macaque PML, failed to detect SV40 in human PML. However, JCV could be detected by in situ hybridization with a JCV-specific DNA probe. Moreover, JCV DNA sequences were amplified by PCR from the human PML tissues, whereas SV40 DNA sequences were amplified only from the macaque brain. Thus, we could not confirm the original reports that the demyelinating agent in these three cases of PML was SV40, rather than JCV. We conclude that SV40 infection of the central nervous system need not be ruled out in the differential diagnosis of PML.
Insights
This study reexamined progressive multifocal leukoencephalopathy (PML) cases initially linked to simian virus 40 (SV40). Researchers found JC virus (JCV), not SV40, was the cause in these PML cases, clarifying viral etiologies.
Area of Science:
- Neurology
- Virology
- Pathology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease.
- PML has been associated with both JC virus (JCV) and simian virus 40 (SV40).
- Previous reports suggested SV40 as an etiological agent in some PML cases.
Purpose of the Study:
- To re-evaluate three human PML cases initially suspected to be caused by SV40.
- To determine the causative viral agent in these PML cases using advanced molecular techniques.
- To clarify the role of SV40 versus JCV in the pathogenesis of PML.
Main Methods:
- Utilized monoclonal antibodies against SV40 capsid antigen VPI.
- Employed virus-specific biotinylated DNA probes for in situ hybridization.
- Applied polymerase chain reaction (PCR) with virus-specific primers.
- Used macaque PML brain tissue as a positive control for SV40 infection.
Main Results:
- SV40 VPI antigen was not detected in the human PML lesions.
- SV40 DNA was not detected in human PML tissues by in situ hybridization or PCR.
- JCV was detected in human PML tissues by in situ hybridization and PCR.
- SV40 DNA was detected only in the macaque control brain tissue.
Conclusions:
- The causative agent in the re-examined PML cases was JCV, not SV40.
- Previous associations of SV40 with these PML cases could not be confirmed.
- SV40 remains a potential, though less common, etiological agent in PML and should be considered in differential diagnoses.