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.

Transitional cell carcinoma of renal allograft associated with BK virus infection

“…BKV is associated with transitional cell carcinoma of the allograft renal pelvis and that warrants monitoring these patients for this possibility. 7 The role for viruses in malignancy includes the expression of viral oncogenes, such as polyomavirus TAg, adenovirus E1a and E1b, and papillomavirus E6 and E7. 8 There is some evidence of the potential role of BKV in cancer.…”

BK polyomavirus association with colorectal cancer development

“…BKV inoculation into animal models causes the development of various neoplasms, including glioma, neuroblastoma, ependymoma, osteosarcoma, liposarcoma, and fibrosarcoma, among others (Tognon et al, 2003). The oncogenic potential of BKV is related to the influential transforming genes involved in growth control and mitogenic signaling encoded in its genome (Khalili et al, 2003;White and Khalili, 2004;Kenan et al, 2015).…”

Human polyomavirus BKV transcriptionally activates DNA methyltransferase 1 through the pRb/E2F pathway

“…DNA tumor virus infection has been implicated in the etiology of many cancers including malignant mesotheliomas, non-Hodgkin's lymphoma and tumors of the bone, brain and urinary tract (Khalili et al, 2003;Tognon et al, 2003;Vilchez and Butel, 2004). The most commonly explored role for viruses in cancer involves the expression of viral oncogenes, such as polyomavirus large T antigens (TAg), adenovirus E1a and E1b, and papillomavirus E6 and E7 (O'Shea, 2005).…”