The two-faced nature of BK polyomavirus: lytic infection or non-lytic large-T-positive carcinoma

J Pathol. 2018 Sep;246(1):7-11. doi: 10.1002/path.5127. Epub 2018 Jul 31.

Abstract

In immunocompromised patients, reactivation of latent BK polyomavirus (BKPyV) can cause disease with lytic infections of the kidneys and the lower urinary tract. Emerging evidence also links BKPyV to oncogenesis and high-grade intrarenal and transitional cell carcinomas. These neoplasms strongly express polyomavirus large-T antigen as a defining feature; that is, they are 'large-T-positive carcinomas'. Such neoplasms arise in immunocompromised patients, typically in renal allograft recipients, and preferentially in tissues harbouring latent BKPyV. In recent articles in this journal, it was shown that tumour cells harbour replication-incompetent clonal BKPyV. The virus can be truncated and randomly integrated into the genome, and/or it can be mutated in an episomal state. Truncation and/or deletions in the BKPyV non-coding control region can hamper late viral gene expression, replication, and cell lysis, while facilitating overexpression of early genes, including that encoding large-T. Biologically active fusion proteins or alterations in human tumour suppressor or promoter function have not been described so far, making uncontrolled large-T gene expression in non-lytically infected cells a prime suspect for neoplastic transformation. Current concepts of BKPyV-induced disease, including recent reports from this journal, are discussed, and evolving paradigms of BKPyV-associated oncogenesis are highlighted. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Keywords: BK polyomavirus; immunosuppression; infection; large-T; neoplasm; oncogenesis; polyomavirus nephropathy; transplantation; urogenital tract.

Publication types

  • Comment

MeSH terms

  • BK Virus / genetics*
  • Carcinogenesis
  • Humans
  • Kidney Transplantation*
  • Polyomavirus Infections*
  • United Kingdom
  • Virus Replication / genetics