Human neurotropic polyomavirus, jcv, and its role in carcinogenesis

ABSTRACT A number of recent studies have reported the detection of the ubiquitous human polyomavirus, JC virus (JCV), in samples derived from several types of neural as well as non-neural

human tumors. The human neurotropic JCV was first identified as the etiologic agent of the fatal demyelinating disease, progressive multifocal leukoencephalopathy, which usually occurs in

individuals with defects in cell-mediated immunity, including AIDS. However, upon mounting evidence of the oncogenic potential of the viral regulatory protein, T-antigen, and JCV's

oncogenecity in a broad range of animal models, studies were initiated to determine its potential involvement in human carcinogenesis. Initially, the most frequently observed tumors in

rodent models, including medulloblastoma, astrocytoma, glioblastoma, and other neural-origin tumors were analysed. These studies were followed by analysis of non-neural tumors such as

colorectal carcinomas. In a subset of each tumor type examined, JC viral genomic DNA sequences could be detected by PCR and confirmed by Southern blot hybridization or direct sequencing. In

a smaller subset of the tumors, the expression of T-antigen was observed by immunohistochemical analysis. Owing to the established functions of T-antigen including its ability to interact

with tumor suppressor proteins such as Rb and p53, and its ability to influence chromosomal stability, potential mechanisms of JCV T-antigen-mediated cellular dysregulation are discussed.

Further, as increasing evidence suggests that T-antigen is not required for maintenance of a transformed phenotype, a hit-and-run model for T-antigen-induced transformation is proposed.

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their insightful discussion, and sharing of ideas of reagents. We also thank C Schriver for preparation of this manuscript. This work was made possible by grants awarded by NIH to JG and KK.

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015-96, Room 203,

Philadelphia, 19122, PA, USA Kamel Khalili, Luis Del Valle, Jessica Otte, Michael Weaver & Jennifer Gordon Authors * Kamel Khalili View author publications You can also search for this

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ARTICLE CITE THIS ARTICLE Khalili, K., Del Valle, L., Otte, J. _et al._ Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. _Oncogene_ 22, 5181–5191 (2003).

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