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Article

Persistent BK Polyomavirus Viruria Is Associated with Accumulation of VP1 Mutations and Neutralization Escape

1
Centre de Recherche en Transplantation et Immunoologie (CRTI), UMR 1064, INSERM, Université de Nantes, 44093 Nantes, France
2
Institut de Transplantation Urologie-Néphrologie (ITUN), CHU Nantes, 44093 Nantes, France
3
Faculté des Sciences et des Techniques, Université de Nantes, 44322 Nantes, France
4
Institut für Virologie, Universität Leipzig, 04103 Leipzig, Germany
5
Service de Virologie, CHU Nantes, 44093 Nantes, France
6
Service de Néphrologie et Immunologie Clinique, CHU Nantes, 44093 Nantes, France
7
Faculté de Médecine, Université de Nantes, 44093 Nantes, France
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(8), 824; https://doi.org/10.3390/v12080824
Received: 19 July 2020 / Revised: 27 July 2020 / Accepted: 28 July 2020 / Published: 29 July 2020
(This article belongs to the Special Issue BK Virus and Transplantation)
To investigate the relationship between neutralization escape and persistent high-level BK polyomavirus replication after kidney transplant (KTx), VP1 sequences were determined by Sanger and next-generation sequencing in longitudinal samples from KTx recipients with persistent high-level viruria (non-controllers) compared to patients who suppressed viruria (controllers). The infectivity and neutralization resistance of representative VP1 mutants were investigated using pseudotype viruses. In all patients, the virus population was initially dominated by wild-type VP1 sequences, then non-synonymous VP1 mutations accumulated over time in non-controllers. BC-loop mutations resulted in reduced infectivity in 293TT cells and conferred neutralization escape from cognate serum in five out of six non-controller patients studied. When taken as a group, non-controller sera were not more susceptible to neutralization escape than controller sera, so serological profiling cannot predict subsequent control of virus replication. However, at an individual level, in three non-controller patients the VP1 variants that emerged exploited specific “holes” in the patient’s humoral response. Persistent high-level BK polyomavirus replication in KTx recipients is therefore associated with the accumulation of VP1 mutations that can confer resistance to neutralization, implying that future BKPyV therapies involving IVIG or monoclonal antibodies may be more effective when used as preventive or pre-emptive, rather than curative, strategies. View Full-Text
Keywords: polyomavirus; transplantation; immunity; neutralization polyomavirus; transplantation; immunity; neutralization
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MDPI and ACS Style

McIlroy, D.; Hönemann, M.; Nguyen, N.-K.; Barbier, P.; Peltier, C.; Rodallec, A.; Halary, F.; Przyrowski, E.; Liebert, U.; Hourmant, M.; Bressollette-Bodin, C. Persistent BK Polyomavirus Viruria Is Associated with Accumulation of VP1 Mutations and Neutralization Escape. Viruses 2020, 12, 824. https://doi.org/10.3390/v12080824

AMA Style

McIlroy D, Hönemann M, Nguyen N-K, Barbier P, Peltier C, Rodallec A, Halary F, Przyrowski E, Liebert U, Hourmant M, Bressollette-Bodin C. Persistent BK Polyomavirus Viruria Is Associated with Accumulation of VP1 Mutations and Neutralization Escape. Viruses. 2020; 12(8):824. https://doi.org/10.3390/v12080824

Chicago/Turabian Style

McIlroy, Dorian, Mario Hönemann, Ngoc-Khanh Nguyen, Paul Barbier, Cécile Peltier, Audrey Rodallec, Franck Halary, Emilie Przyrowski, Uwe Liebert, Maryvonne Hourmant, and Céline Bressollette-Bodin. 2020. "Persistent BK Polyomavirus Viruria Is Associated with Accumulation of VP1 Mutations and Neutralization Escape" Viruses 12, no. 8: 824. https://doi.org/10.3390/v12080824

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