Oncogenic transformation by BK virus and association with human tumors

Abstract

BK virus (BKV), a human polyomavirus closely related to JC virus and Simian Virus 40, is ubiquitous in human populations worldwide. After primary infection, BKV establishes a lifelong latent infection in many organs. BKV transforms rodent cells to the neoplastic phenotype and is highly oncogenic in rodents. This review considers the oncogenic potential of BKV in humans and its possible involvement in human tumors. BKV sequences and T antigen (Tag) are detected in several types of human neoplasms, although the viral load is generally low, with less than one copy of the viral genome per cell. The possible causative role of BKV in human oncogenesis rests on the ability of BKV Tag to inactivate the functions of tumor suppressor proteins p53 and pRB family as well as on its ability to induce chromosomal aberrations in human cells. A 'hit and run' mechanism and secretion of paracrine growth factors by BKV Tag-positive cells, recruiting into proliferation neighboring and distant cells, are discussed as possible BKV pathogenic elements in human oncogenesis.

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

“…The occurrence of a statistically significant increase of CNS and non-CNS tumor incidence, as well as the presence of viral DNA in those patients, confers to JCV the status of tumor virus Reiss and Khalili, 2003). Similarly to JCV, BKV is widely spread among the human population and its sequences and T antigen are detected in several types of human neoplasms (Tognon et al, 2003).…”

Detection and expression of human BK virus sequences in neoplastic prostate tissues

“…These observations have led researchers to speculate that an infectious agent might play a role in PCA (McNicol and Dodd, 1991;Ibrahim et al, 1992;Rotola et al, 1992;Cuzik, 1995;Noda et al, 1998). Polyomaviruses are candidates for this agent, although the etiological role of polyomaviruses in human tumors remains debated despite several reports demonstrating the presence and expression of sequences from these viruses (Imperiale, 2000(Imperiale, , 2001; Reploeg et al, 2001;Tognon et al, 2003).…”

Lack of BK virus DNA sequences in most transitional‐cell carcinomas of the bladder

“…BKV codes for a nonstructural protein, the large tumor antigen (T-Ag), which can bind to and inactivate tumor suppressor proteins p53 and pRb, resulting in aberrant cell cycle regulation. 17,18 BKV DNA can transform embryonic human fibroblasts (reviewed in Ref. 19), and BKV-associated cytologic changes in the urothelium can mimic high-grade transitional cell carcinoma cytology in transplant patients.…”