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Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal
H Takahashi1, Y Yogo, Y Furuta
1Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.
Insights
This study reports a rare case of cerebellar progressive multifocal leukoencephalopathy (PML) in a Japanese patient on hemodialysis. The JC virus (JCV) DNA analysis revealed genetic links to archetypal JCV isolates in Japan.
Area of Science:
- Neuroscience
- Virology
- Genetics
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system.
- JC virus (JCV) typically affects the cerebrum, but cerebellar involvement is exceptionally rare.
Observation:
- A rare case of cerebellar PML was observed in a Japanese patient undergoing long-term hemodialysis.
- JC virus (JCV) DNA was molecularly cloned and analyzed from the patient's tissue.
Findings:
- Nine out of ten cloned JCV DNA samples, designated Sap-1, exhibited identical restriction endonuclease fragment patterns.
- The regulatory regions of Sap-1 JCV isolates showed structural similarities to those from cerebral PML cases.
- Genetic analysis indicated that Sap-1 is related to an archetypal JCV isolate found in Japan.
Implications:
- This case expands the understanding of JCV tissue tropism and the clinical spectrum of PML.
- The findings suggest potential geographical or host-related factors influencing JCV pathogenesis.
- Further research into JCV genetic variations may elucidate mechanisms of PML development in specific patient populations.