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Detection of JC Virus DNA Sequences and Expression of the Viral Regulatory Protein T-Antigen in Tumors of the Central Nervous System¹

Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122 [L. D. V., J. G., S. E., S. C., K. K.]; Department of Anatomy, University of Patras School of Medicine, GR-26500 Patras, Greece [M. A., J. N. V.]; Department of Histopathology and Morbid Anatomy, Queen Mary, University of London, London E1 4NS, United Kingdom [J. F. G.]; Department of Pediatrics, Medical College of Pennsylvania Hahnemann University and St. Christopher’s Hospital for Children, Philadelphia, Pennsylvania 19134 [C. D. K.]; and Department of Pathology and Laboratory Medicine, Medical College of Pennsylvania Hahnemann University, Philadelphia, Pennsylvania 19102 [S. C.]

JC virus (JCV) is a neurotropic polyomavirus infecting greater than 70% of the human population worldwide during early childhood. Replication of JCV in brains of individuals with impaired immune systems results in the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Furthermore, JCV possesses an oncogenic potential and induces development of various neuroectodermal origin tumors including medulloblastomas and glioblastomas in experimental animals. The oncogenecity of JCV is attributed to the viral early gene product, T-antigen, which has the ability to associate with and functionally inactivate well-studied tumor suppressor proteins including p53 and pRb. The observations from laboratory animal experiments have provided a rationale for examining the presence of the JCV DNA sequence and expression of the viral oncogenic protein in human brain tumors. We have examined 85 clinical specimens from the United Kingdom, Greece, and the United States, representing various human brain tumors including oligodendroglioma, astrocytoma, pilocytic astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma multiforme, gliomatosis cerebri, gliosarcoma, ependymoma, and subependymoma, for their possible association with JCV. We performed gene amplification techniques using a pair of primers that recognize the JCV DNA sequence, and we demonstrated the presence of the viral early sequence in 49 (69%) of 71 samples. More importantly, our results from immunohistochemistry analysis revealed expression of JCV T-antigen in the nuclei of tumor cells in 28 (32.9%) of 85 tested samples. These observations, along with earlier in vitro and in vivo data on the transforming ability of this human neurotropic virus invite additional studies to re-evaluate the role of JCV in the pathogenesis of human brain tumors.

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