ReviewBK virus and human cancer: Innocent until proven guilty
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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These authors contributed equally to this work.