Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution

Alberto Peretti, Eileen M. Geoghegan, Diana V. Pastrana, Sigrun Smola, Pascal Feld, Marlies Sauter, Stefan Lohse, Mayur Ramesh, Efrem S. Lim, David Wang, Cinzia Borgogna, Peter C. FitzGerald, Valery Bliskovsky, Gabriel J. Starrett, Emily K. Law, Reuben S. Harris, J. Keith Killian, Jack Zhu, Marbin Pineda, Paul S. MeltzerRenzo Boldorini, Marisa Gariglio, Christopher B. Buck

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

BK polyomavirus (BKV) frequently causes nephropathy (BKVN) in kidney transplant recipients (KTRs). BKV has also been implicated in the etiology of bladder and kidney cancers. We characterized BKV variants from two KTRs who developed BKVN followed by renal carcinoma. Both patients showed a swarm of BKV sequence variants encoding non-silent mutations in surface loops of the viral major capsid protein. The temporal appearance and disappearance of these mutations highlights the intra-patient evolution of BKV. Some of the observed mutations conferred resistance to antibody-mediated neutralization. The mutations also modified the spectrum of receptor glycans engaged by BKV during host cell entry. Intriguingly, all observed mutations were consistent with DNA damage caused by antiviral APOBEC3 cytosine deaminases. Moreover, APOBEC3 expression was evident upon immunohistochemical analysis of renal biopsies from KTRs. These results provide a snapshot of in-host BKV evolution and suggest that APOBEC3 may drive BKV mutagenesis in vivo. BK polyomavirus causes nephropathy in kidney transplant patients. Peretti et al. show that, during the development of nephropathy, BKV acquires mutations that confer a selective advantage to the virus. The sequence changes are suggestive of a role for cellular APOBEC3 DNA cytosine deaminases in driving BKV mutagenesis in vivo.

Original languageEnglish
Pages (from-to)628-635.e7
JournalCell Host and Microbe
Volume23
Issue number5
DOIs
StatePublished - May 9 2018

Keywords

  • APOBEC
  • APOBEC3
  • BKPyV
  • JCPyV
  • JCV
  • bladder
  • carcinoma
  • human polyomavirus
  • urothelial

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    Peretti, A., Geoghegan, E. M., Pastrana, D. V., Smola, S., Feld, P., Sauter, M., Lohse, S., Ramesh, M., Lim, E. S., Wang, D., Borgogna, C., FitzGerald, P. C., Bliskovsky, V., Starrett, G. J., Law, E. K., Harris, R. S., Killian, J. K., Zhu, J., Pineda, M., ... Buck, C. B. (2018). Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution. Cell Host and Microbe, 23(5), 628-635.e7. https://doi.org/10.1016/j.chom.2018.04.005