Cell Host & Microbe
Volume 23, Issue 5, 9 May 2018, Pages 628-635.e7
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Short Article
Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution

https://doi.org/10.1016/j.chom.2018.04.005Get rights and content
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Highlights

  • BKV variants sequenced from kidney transplant patients during development of nephropathy

  • BKV major capsid protein acquires surface loop mutations over time

  • Mutations confer resistance to neutralizing antibodies and modify glycan receptor usage

  • Mutational signatures match APOBEC3 activity, and renal biopsies are positive for APOBEC3

Summary

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.

Keywords

human polyomavirus
carcinoma
BKPyV
JCV
JCPyV
APOBEC
APOBEC3
urothelial
bladder

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