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Thomas Flaig, MD

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Evaluating the Risk of BK Polyomavirus Infection During Childhood and Future Bladder Cancer

By: Joseph Fanelli
Posted: Wednesday, April 27, 2022

According to research findings presented in Oncogene, reactivated cases of BK polyomavirus infections in adults may be a possible risk factor for bladder cancer in immune-insufficient patients such as those with transplants and the elderly. Jennifer Southgate, PhD, of the University of York, Heslington, England, and colleagues provided mechanistic evidence that BK polyomavirus can infect and leave apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC)-induced damage in the urothelial genome.

“This research is critically needed to improve our understanding of why people who are immunosuppressed, such as transplant patients, get more bladder cancers,” said coauthor Simon C. Baker, PhD, of the University of York, in an institutional press release. “Our research should not only help improve the care we give to these patients, but it may also have much wider implications for preventing bladder cancer in the future.”

In this study, the authors used a mitotically quiescent, functionally differentiated model of normal human urothelium to examine cases of BK polyomavirus infections. After analysis, the researchers found that BK polyomavirus infection led to significantly elevated APOBEC3A and APOBEC3B protein, an increase in deaminase activity, and greater numbers of apurinic and apyrimidinic sites in the host urothelial genome. The BK polyomavirus large T antigen stimulated reentry from G0 into the cell cycle through the inhibition of retinoblastoma protein and activation of the EZH2, E2F1, and FOXM1 genes, with cells arresting in G2.

The authors observed that the single-stranded DNA displacement loops formed in urothelial cells during BK polyomavirus infection interacted with large T antigen to supply a substrate for APOBEC3 activity. In addition, the inclusion of interferon gamma to infected urothelium suppressed expression of the viral genome, the researchers explained.

Disclosure: The study authors reported no conflicts of interest.


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