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Detection of JC Polyomavirus DNA Sequences and Cellular Localization of T-Antigen and Agnoprotein in Oligodendrogliomas¹

Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122 [L. D. V., S. E., C. L., K. K.]; Departmento de Patología, The American British Cowdray Medical Center I.A.P., México D.F., México 01120 [C. O-H.]; and Department of Pediatrics, MCP-Hahnemann University and Departments of Pediatrics and Pathology, St. Christopher’s Hospital for Children, Philadelphia, Pennsylvania 19134 [C. D. K.]

Purpose: Productive infection of the human neurotropic polyomavirus JCPyV in oligodendrocytes leads to the development of progressive multifocal leukoencephalopathy, a fatal demyelinating disorder of the central nervous system. In addition to its role in viral infection, JCPyV T-antigen can transform cells in vitro and induce tumors in experimental animals in the absence of viral DNA replication and late gene expression. The goal of this study is to examine the presence of JCPyV DNA sequences and viral antigens in a series of human oligodendrogliomas.

Experimental Design: A total of 20 well-characterized oligodendrogliomas were examined for detection of the JCPyV genome by PCR and immunohistochemistry for expression of viral proteins.

Results: Gene amplification has revealed the presence of JCPyV DNA sequences corresponding to the NH₂-terminal of T-antigen in 15 of 20 samples. DNA sequences corresponding to late regions, which are responsible for production of the capsid protein, VP1, were detected in 14 of 20 samples. Sequencing of the viral control region determined the presence of JCPyV Mad-4 or JCPyV_CY in these tumors. By immunohistochemistry, T-antigen expression was detected in the nuclei of tumor cells from 10 samples that also contained corresponding DNA sequences by PCR. Eleven of 20 tumors exhibited immunoreactivity for the late auxiliary gene product, agnoprotein. None of the samples showed immunoreactivity for the capsid proteins, ruling out productive infection of neoplastic cells by JCPyV.

Conclusions: Collectively, these observations provide new evidence in support of the association of the oncogenic human neurotropic JCPyV and oligodendrogliomas.