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Case Reports
. 2017 Jun;17(6):1674-1680.
doi: 10.1111/ajt.14191. Epub 2017 Feb 21.

BK Polyomavirus Genomic Integration and Large T Antigen Expression: Evolving Paradigms in Human Oncogenesis

D J Kenan  1 , P A Mieczkowski  2 , E Latulippe  3 , I Côté  4 , H K Singh  1 , V Nickeleit  1
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Free article
Case Reports

BK Polyomavirus Genomic Integration and Large T Antigen Expression: Evolving Paradigms in Human Oncogenesis

D J Kenan et al. Am J Transplant. 2017 Jun.
Free article

Abstract

Human polyomaviruses are ubiquitous, with primary infections that typically occur during childhood and subsequent latency that may last a lifetime. Polyomavirus-mediated disease has been described in immunocompromised patients; its relationship to oncogenesis is poorly understood. We present deep sequencing data from a high-grade BK virus-associated tumor expressing large T antigen. The carcinoma arose in a kidney allograft 6 years after transplantation. We identified a novel genotype 1a BK polyomavirus, called Chapel Hill BK polyomavirus 2 (CH-2), that was integrated into the BRE gene in chromosome 2 of tumor cells. At the chromosomal integration site, viral break points were found, disrupting late BK gene sequences encoding capsid proteins VP1 and VP2/3. Immunohistochemistry and in situ hybridization studies demonstrated that the integrated BK virus was replication incompetent. We propose that the BK virus CH-2 was integrated into the human genome as a concatemer, resulting in alterations of feedback loops and overexpression of large T antigen. Collectively, these findings support the emerging understanding that viral integration is a nearly ubiquitous feature in polyomavirus-associated malignancy and that unregulated large T antigen expression drives a proliferative state that is conducive to oncogenesis. Based on the current observations, we present an updated model of polyomavirus-mediated oncogenesis.

Keywords: basic (laboratory) research/science; cancer/malignancy/neoplasia; clinical research/practice; infection and infectious agents; infectious disease; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; molecular biology: DNA; pathology/histopathology; viral: BK/JC/polyoma.

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