Review
BK virus and human cancer: Innocent until proven guilty

https://doi.org/10.1016/j.semcancer.2009.02.004Get rights and content

Abstract

BK virus (BKV) is a polyomavirus that ubiquitously infects the human population. Following a typically subclinical primary infection, BKV establishes a life-long persistent infection in the kidney and urinary tract. BKV is known to reactivate and cause severe disease in immunosuppressed patients, particularly renal and bone marrow transplant patients. Infection of BKV in rodent animal models or cells in culture often results in tumor formation or transformation, respectively. When co-expressed with activated oncogenes, BKV large tumor antigen drives the transformation of primary human cells. An etiological role of BKV in human cancer, however, remains controversial. Multiple reports have demonstrated conflicting results in regards to the presence of BKV sequences and/or proteins in various tumor types. This review compiles the most recent findings of BKV detection in a number of human cancers. Due to the lack of conclusive causality data from these studies, there does not appear to be a definitive association between BKV and human cancers.

Section snippets

BK virus infection in humans

The life cycle of BKV begins with the interaction of the capsid protein VP1 with cellular ganglioside receptors [12]. The virus then enters the cell through caveolae-mediated endocytosis, passes through a yet-to-be-defined acidic compartment and the caveosome, travels along the microtubule network, and finally reaches the endoplasmic reticulum (ER) [13], [14], [15]. Viral uncoating is likely to occur in the ER, which finally leads to the delivery of the genome into the nucleus and subsequent

Oncogenicity of BK virus

BKV has been implicated as a tumor virus because of its behavior in vitro and in animal models. Expression of the BKV early region oncogenically transforms rodent cells in culture and immortalizes human cells alone or in the presence of other oncogenes including ras, myc and adenovirus E1A [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62]. Inoculation of BKV into young or newborn hamsters, mice, and rats leads to the development of several different types

BK virus and human tumors

Reports of the presence or absence of BKV sequences and proteins in human tumors have been accumulating over the past three decades. Technological advances in polymerase chain reaction (PCR) have made it possible to detect DNA and RNA in small biopsy samples with a high degree of sensitivity, and to distinguish BKV sequences from those of JCV and SV40. Extreme care must be taken, however, when using a PCR-based assay to detect viral sequences. Increasing the number of PCR cycles to develop a

Conclusions

The clinical studies described above have demonstrated both the presence and absence of BKV sequences in cancerous tissues. As a member of the polyomavirus family, it can be stated that BKV has all the qualifications to be a cofactor in the induction and/or progression of human tumors. A causal role for BKV in human neoplasia, however, still remains to be established. There are several concerns when considering a role for BKV in carcinogenesis: (a) BKV DNA sequences are often found in normal

Conflict of interest

There are no conflicts of interest.

Acknowledgements

We thank members of the Imperiale lab for critical review of the manuscript. This work was supported by AI060584 and CA118970 awarded to M.J.I. from the NIH. J.R.A. was supported by the F.G. Novy Fellowship. M.J. was supported by the American Heart Association Postdoctoral Fellowship 0825806G.

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