Detection of JC virus DNA sequences and expression of the viral regulatoryprotein T-antigen in tumors of the central nervous system

JC virus (JCV) is a neurotropic polyomavirus infecting greater than 70% of the human population worldwide during early childhood. Replication of JCV i n brains of individuals with impaired immune systems results in the fatal d emyelinating disease, progressive multifocal leukoencephalopathy (PML), Fur thermore, JCV possesses an oncogenic potential and induces development of v arious neuroectodermal origin tumors including medulloblastomas and gliobla stomas in experimental animals. The oncogenecity of JCV is attributed to th e viral early gene product, T-antigen, which has the ability to associate w ith and functionally inactivate well-studied tumor suppressor proteins incl uding p53 and pRb. The observations from laboratory animal experiments have provided a rationale for examining the presence of the JCV DNA sequence an d expression of the viral oncogenic protein in human brain tumors. We have examined 85 clinical specimens from the United Kingdom, Greece, and the Uni ted States, representing various human brain tumors including oligodendrogl ioma, astrocytoma, pilocytic astrocytoma, oligoastrocytoma, anaplastic astr ocytoma, anaplastic oligodendroglioma, glioblastoma multiforme, gliomatosis cerebri, gliosarcoma, ependymoma, and subependymoma, for their possible as sociation with JCV. We performed gene amplification techniques using a pair of primers that recognize the JCV DNA sequence, and we demonstrated the pr esence of the viral early sequence in 49 (69%) of 71 samples. More importan tly, our results from immunohistochemistry analysis revealed expression of JCV T-antigen in the nuclei of tumor cells in 28 (32.9%) of 85 tested sampl es. These observations, along with earlier in vitro and in vivo data on the transforming ability of this human neurotropic virus invite additional stu dies to re-evaluate the role of JCV in the pathogenesis of human brain tumo rs.