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 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

10 Citations (Scopus)

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 (US)
Pages (from-to)628-635.e7
JournalCell Host and Microbe
DOIs
StateAccepted/In press - May 9 2018
Externally publishedYes

Fingerprint

BK Virus
Viruses
Kidney
Mutation
Cytosine Deaminase
Mutagenesis
Transplant Recipients
Kidney Neoplasms
Capsid Proteins
Urinary Bladder Neoplasms
DNA Damage
Antiviral Agents
Polysaccharides

Keywords

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

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Peretti, A., Geoghegan, E. M., Pastrana, D. V., Smola, S., Feld, P., Sauter, M., ... Buck, C. B. (Accepted/In press). Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution. Cell Host and Microbe, 628-635.e7. https://doi.org/10.1016/j.chom.2018.04.005

Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution. / Peretti, Alberto; Geoghegan, Eileen M.; Pastrana, Diana V.; Smola, Sigrun; Feld, Pascal; Sauter, Marlies; Lohse, Stefan; Ramesh, Mayur; Lim, Efrem; Wang, David; Borgogna, Cinzia; FitzGerald, Peter C.; Bliskovsky, Valery; Starrett, Gabriel J.; Law, Emily K.; Harris, Reuben S.; Killian, J. Keith; Zhu, Jack; Pineda, Marbin; Meltzer, Paul S.; Boldorini, Renzo; Gariglio, Marisa; Buck, Christopher B.

In: Cell Host and Microbe, 09.05.2018, p. 628-635.e7.

Research output: Contribution to journalArticle

Peretti, A, Geoghegan, EM, Pastrana, DV, Smola, S, Feld, P, Sauter, M, Lohse, S, Ramesh, M, Lim, E, Wang, D, Borgogna, C, FitzGerald, PC, Bliskovsky, V, Starrett, GJ, Law, EK, Harris, RS, Killian, JK, Zhu, J, Pineda, M, Meltzer, PS, Boldorini, R, Gariglio, M & Buck, CB 2018, 'Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution', Cell Host and Microbe, pp. 628-635.e7. https://doi.org/10.1016/j.chom.2018.04.005
Peretti, Alberto ; Geoghegan, Eileen M. ; Pastrana, Diana V. ; Smola, Sigrun ; Feld, Pascal ; Sauter, Marlies ; Lohse, Stefan ; Ramesh, Mayur ; Lim, Efrem ; Wang, David ; Borgogna, Cinzia ; FitzGerald, Peter C. ; Bliskovsky, Valery ; Starrett, Gabriel J. ; Law, Emily K. ; Harris, Reuben S. ; Killian, J. Keith ; Zhu, Jack ; Pineda, Marbin ; Meltzer, Paul S. ; Boldorini, Renzo ; Gariglio, Marisa ; Buck, Christopher B. / Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution. In: Cell Host and Microbe. 2018 ; pp. 628-635.e7.
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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.",
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T1 - Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution

AU - Peretti, Alberto

AU - Geoghegan, Eileen M.

AU - Pastrana, Diana V.

AU - Smola, Sigrun

AU - Feld, Pascal

AU - Sauter, Marlies

AU - Lohse, Stefan

AU - Ramesh, Mayur

AU - Lim, Efrem

AU - Wang, David

AU - Borgogna, Cinzia

AU - FitzGerald, Peter C.

AU - Bliskovsky, Valery

AU - Starrett, Gabriel J.

AU - Law, Emily K.

AU - Harris, Reuben S.

AU - Killian, J. Keith

AU - Zhu, Jack

AU - Pineda, Marbin

AU - Meltzer, Paul S.

AU - Boldorini, Renzo

AU - Gariglio, Marisa

AU - Buck, Christopher B.

PY - 2018/5/9

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N2 - 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.

AB - 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.

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KW - APOBEC3

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KW - carcinoma

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KW - JCV

KW - urothelial

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