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Isolation and characterization of a type II JC virus from a brain biopsy of a patient with PML
P W Zoltick1, R P Mayreddy, C F Chang
1Department of Biochemistry & Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Abstract:
Brain tissue of a patient with multiple myeloma suffering from neurological disorders similar to those seen in progressive multifocal leukoencephalopathy (PML) patients was evaluated for the presence of the papovavirus, JCV. Results from polymerase chain reaction (PCR) revealed the presence of JCV with structural organization at the control region which is distinct from well-characterized isolates, ie Mad-1 and Mad-4. The control region of the new isolate, named JCVPhila-1' contains a 22 nucleotide insertion which separates the TATA box from the NF-1 regulatory motif. Only 18 nucleotides of the insert are duplicated in the second copy of the enhancer/promoter of the new isolate, which is 84 nucleotides in size. Results from a transcription assay indicate a modest elevated level of JCVPhila-1 early promoter activity compared to that of JCVMad-4 in glial cell lines. The basal and T-antigen-induced transcriptional activities of the JCVPhila-1 late promoter was lower with respect to Mad-4 late gene activity in glial cells. Of particular interest was the observation that in the cells producing the early protein, T-antigen, JCVPhila-1 DNA replicated more efficiently then the Mad-4 DNA. These results suggest that the alterations seen in the JCVPhila-1 control region may differentially influence early and late gene expression and facilitate amplification of the viral genome in cells derived from the CNS.
Insights
A novel strain of John Cunningham virus (JCV), JCVPhila-1, was identified in a multiple myeloma patient with neurological symptoms. This JCV strain exhibits unique control region alterations potentially affecting viral gene expression and replication in the central nervous system (CNS).
Area of Science:
- Neurovirology
- Molecular Virology
- Genetics
Background:
- Investigating John Cunningham virus (JCV) in patients with multiple myeloma and neurological disorders.
- Comparing a novel JCV isolate (JCVPhila-1) to known strains (Mad-1, Mad-4).
Observation:
- JCVPhila-1 possesses a distinct control region with a 22-nucleotide insertion, separating key regulatory elements.
- The enhancer/promoter region of JCVPhila-1 shows partial duplication of this insert.
- Transcription assays revealed altered promoter activities for JCVPhila-1 compared to JCVMad-4.
Findings:
- JCVPhila-1 demonstrates modestly elevated early promoter activity but lower late promoter activity in glial cells.
- Viral DNA replication of JCVPhila-1 is more efficient than Mad-4 in cells expressing the T-antigen.
- The unique control region of JCVPhila-1 may influence differential gene expression and viral genome amplification.
Implications:
- The findings suggest that specific mutations in the JCV control region can modulate viral gene expression and replication dynamics.
- This research provides insights into the molecular mechanisms underlying JCV pathogenesis in the central nervous system.
- Understanding these alterations is crucial for developing targeted therapeutic strategies against JCV-associated neurological diseases.