@article{293fa69a8e4e4ba3a861b14c63c28154,
title = "Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution",
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.",
keywords = "APOBEC, APOBEC3, BKPyV, JCPyV, JCV, bladder, carcinoma, human polyomavirus, urothelial",
author = "Alberto Peretti and Geoghegan, {Eileen M.} and Pastrana, {Diana V.} and Sigrun Smola and Pascal Feld and Marlies Sauter and Stefan Lohse and Mayur Ramesh and Lim, {Efrem S.} and David Wang and Cinzia Borgogna and FitzGerald, {Peter C.} and Valery Bliskovsky and Starrett, {Gabriel J.} and Law, {Emily K.} and Harris, {Reuben S.} and Killian, {J. Keith} and Jack Zhu and Marbin Pineda and Meltzer, {Paul S.} and Renzo Boldorini and Marisa Gariglio and Buck, {Christopher B.}",
note = "Funding Information: This work was funded by the NIH Intramural Research Program and supported by grants from San Paolo Company (grant CSP 2014 to C.B.) and Italian Association for Cancer Research (AIRC; grant IG 2012 to M.G.). Salary support for A.P. was provided by the Italian Foundation for Cancer Research (FIRC; Fellowship for Abroad 2013). We gratefully acknowledge Antonio Amoroso (University of Turin, Italy) for providing pre-transplantation and donor sera for Pt1 and Pt2. Salary support for G.J.S. is provided by a National Science Foundation (NSF) Graduate Research Fellowship ( 00039202 ). R.S.H. is an investigator of the Howard Hughes Medical Institute (HHMI). Funding Information: This work was funded by the NIH Intramural Research Program and supported by grants from San Paolo Company (grant CSP 2014 to C.B.) and Italian Association for Cancer Research (AIRC; grant IG 2012 to M.G.). Salary support for A.P. was provided by the Italian Foundation for Cancer Research (FIRC; Fellowship for Abroad 2013). We gratefully acknowledge Antonio Amoroso (University of Turin, Italy) for providing pre-transplantation and donor sera for Pt1 and Pt2. Salary support for G.J.S. is provided by a National Science Foundation (NSF) Graduate Research Fellowship (00039202). R.S.H. is an investigator of the Howard Hughes Medical Institute (HHMI). Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = may,
day = "9",
doi = "10.1016/j.chom.2018.04.005",
language = "English (US)",
volume = "23",
pages = "628--635.e7",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}