Polyomavirus BK and prostate cancer: a complex interaction of potential clinical relevance

Abstract

Several studies associating BK polyomavirus (BKPyV) and prostate cancer (PCa) suggested that this virus may exert its oncogenic activity at early stages of cancer development. The BKPyV oncogene, the large T antigen (LTag), has frequently been detected in areas of proliferative inflammatory atrophy, which is considered a precursor lesion leading to prostatic intraepithelial neoplasia and overt PCa. In a recently updated systematic review, the presence of BKPyV was significantly higher in PCa tissues than in healthy control tissues, providing an indication for a link between BKPyV infection and cancer risk. In addition, recent original investigations highlighted an association between expression of the virus and the clinical course of PCa. For example, by studying immune responses elicited against BKPyV LTag, a significant association between LTag positive cancer lesions and a peculiar regulatory profiling has been observed in PCa patients with evidence of disease recurrence after surgical radical prostatectomy. Lastly, a study carried out in a larger cohort of patients undergoing radical prostatectomy revealed the IgG response against LTag as an independent predictor of disease recurrence. Although a full picture of the mechanisms potentially responsible for the involvement of BKPyV in PCa is not available yet, continuing work on this topic should help to refine the potential role of BKPyV in PCa patients, perhaps revealing unsuspected associations with the clinical course of this disease.

Specific IgG Antibodies React to Mimotopes of BK Polyomavirus, a Small DNA Tumor Virus, in Healthy Adult Sera

“…These Tag and tag activities are able to adversely affect the cellular genome where gene mutations may accumulate. Due to Tag binding, in the absence of p53 functions, the cellular DNA then remains unrepaired and consequently the genome “derails” (3, 10). In addition, it has been shown that, in prostate carcinoma (PCa), loss-of function mutations in the p53 gene at very early stages are rare.…”

“…These mechanisms may ensure PCa genetic heterogeneity. However, at present, there are insufficient human epidemiological data to support this hypothesis (10). Considering that BKPyV infection is ubiquitous in the general population with a prevalence of serum antibodies against this polyomavirus of up to 90% worldwide (2, 5, 6), it is difficult to assess whether this virus has a specific role of in cellular transformation (12).…”

Harnessing systemic immune responses for polyomavirus BK involvement in cancer development and progression

“…These studies are mostly using the middle T oncogene, which is expressed in murine but not in human polyomaviruses. Last but not least, the assertion "the higher the viral load, the higher the risk of cancer development" is misleading because cancer transformation can occur in infected cells during the latent state of BKPyV due to abortive infections [4]. In BKPyV-related human cancer, the established regulatory environment characterizing these malignancies might be maintained or enhanced by BKPyV.…”

The Potential Therapeutic Usefulness of Targeting BK Polyomavirus in Prostate Cancer

“…The detection of the virus at molecular levels in tumor specimens correlates with BKPyV-specific immune responses that might be involved in the progression of PCa [11]. Indeed, in PCa patients with evidence of disease recurrence and BKPyV-positive tumors, the LTag induced an immune tolerogenic response able to sustain the malignancy and favor a bad prognosis [12].…”