Related Experiment Videos
Expression of JC virus T-antigen in a patient with MS and glioblastoma multiforme
L Del Valle1, S Delbue, J Gordon
1Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Objective:
To investigate the presence of human polyomavirus JC virus genome and the expression of the viral oncoprotein T-antigen in neoplastic cells of a patient with MS and a glioblastoma multiforme.
Background:
The postmortem examination of an immunocompetent patient with a neurologic disorder revealed the concurrence of MS plaques in the white matter of the brain and a glioblastoma multiforme in the region of the thalamus.
Methods And Results:
PCR analysis of DNA from demyelinated plaques and the tumor area using primers derived from specific regions of the JC virus genome revealed the presence of viral DNA corresponding to the viral early and late genes. Further examination of the samples for the JC virus regulatory region identified the presence of sequences identical to JC virus Mad-4 and JC virus W1 viral isolates in the tumor and the demyelinated regions. Results from immunohistochemistry showed the detection of the viral early protein, T-antigen, and the cellular tumor suppressor protein, p53, in the nuclei of neoplastic cells. Interestingly, expression of T-antigen, but not p53, was observed in neurofilament-positive cells with neuronal morphology and in glial fibrillary acidic protein-positive astrocytes in the cortex juxtaposed to the MS plaques. Examination of viral late gene expression by immunohistochemistry showed no evidence for viral capsid proteins, thus ruling out productive replication of JC virus in the tumor and MS demyelinated plaques.
Conclusions:
These observations provide molecular and clinical evidence of the association of JC virus in the brain of a patient with concurrent glioblastoma multiforme and MS.
Insights
The JC virus genome and T-antigen were found in the brain of a patient with both multiple sclerosis (MS) and glioblastoma multiforme. This suggests a potential association between JC virus and these neurological conditions.
Area of Science:
- Neurovirology
- Oncology
- Neuropathology
Background:
- Investigated a rare case of concurrent multiple sclerosis (MS) and glioblastoma multiforme (GBM) in an immunocompetent patient.
- Examined the presence and expression of the human polyomavirus JC virus (JCV) in affected brain tissues.
Observation:
- JC virus DNA was detected in both demyelinated plaques and the glioblastoma tumor.
- Specific JCV regulatory sequences, matching Mad-4 and W1 isolates, were identified in the tumor and MS lesions.
Findings:
- The viral oncoprotein T-antigen was expressed in neoplastic cells and in neurons and astrocytes near MS plaques.
- While T-antigen was present, viral capsid proteins were absent, indicating no productive JCV replication.
- The tumor suppressor protein p53 was detected in neoplastic cells, but its expression was not linked to T-antigen presence.
Implications:
- Provides molecular and clinical evidence linking JC virus to the brain in patients with concurrent glioblastoma and MS.
- Suggests a potential role for JC virus in the pathogenesis of either or both conditions.
- Highlights the need for further research into JCV's involvement in neurological diseases.