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Article

Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo

by
Dorian McIlroy
1,2,*,
Cécile Peltier
1,
My-Linh Nguyen
3,
Louise Manceau
1,4,
Lenha Mobuchon
5,
Nicolas Le Baut
1,
Ngoc-Khanh Nguyen
1,
Minh-Chau Tran
3,
The-Cuong Nguyen
6 and
Céline Bressollette-Bodin
1,4
1
Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, Nantes Université, CHU Nantes, INSERM, F-44000 Nantes, France
2
Faculté des Sciences et des Techniques, Nantes Université, 44093 Nantes, France
3
Department of Medical Microbiology, Hanoi Medical University, Hanoi 116001, Vietnam
4
CHU Nantes, Nantes Université, Service de Virologie, 44093 Nantes, France
5
Molecular Biology and Sequencing Services, CHU Nantes, 44000 Nantes, France
6
Department of Kidney Diseases and Dialysis, Vietduc University Hospital, Hanoi 110214, Vietnam
*
Author to whom correspondence should be addressed.
Viruses 2022, 14(9), 2077; https://doi.org/10.3390/v14092077
Submission received: 11 August 2022 / Revised: 2 September 2022 / Accepted: 9 September 2022 / Published: 19 September 2022
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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Abstract

Mutations in the BK polyomavirus (BKPyV) capsid accumulate in kidney transplant (KTx) recipients with persistent virus replication. They are associated with neutralization escape and appear to arise as a result of cytosine deamination by host cell APOBEC3A/B enzymes. To study the mutagenic processes occurring in patients, we amplified the typing region of the VP1 gene, sequenced the amplicons to a depth of 5000–10,000×, and identified rare mutations, which were fitted to COSMIC mutational signatures. Background mutations were identified in amplicons from plasmids carrying the BKPyV genome and compared to mutations observed in 148 samples from 23 KTx recipients in France and in Vietnam. Three mutational signatures were consistently observed in urine, serum, and kidney biopsy samples, two of which, SBS2 and SBS13, corresponded to APOBEC3A/B activity. In addition, a third signature with no known etiology, SBS89, was detected both in patient samples, and in cells infected in vitro with BKPyV. Quantitatively, APOBEC3A/B mutation rates in urine samples were strongly correlated with urine viral load, and also appeared to vary between individuals. These results confirm that APOBEC3A/B is a major, but not the only, source of BKPyV genome mutations in patients.
Keywords: APOBEC; innate immunity; polyomavirus; virus evolution APOBEC; innate immunity; polyomavirus; virus evolution

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MDPI and ACS Style

McIlroy, D.; Peltier, C.; Nguyen, M.-L.; Manceau, L.; Mobuchon, L.; Le Baut, N.; Nguyen, N.-K.; Tran, M.-C.; Nguyen, T.-C.; Bressollette-Bodin, C. Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo. Viruses 2022, 14, 2077. https://doi.org/10.3390/v14092077

AMA Style

McIlroy D, Peltier C, Nguyen M-L, Manceau L, Mobuchon L, Le Baut N, Nguyen N-K, Tran M-C, Nguyen T-C, Bressollette-Bodin C. Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo. Viruses. 2022; 14(9):2077. https://doi.org/10.3390/v14092077

Chicago/Turabian Style

McIlroy, Dorian, Cécile Peltier, My-Linh Nguyen, Louise Manceau, Lenha Mobuchon, Nicolas Le Baut, Ngoc-Khanh Nguyen, Minh-Chau Tran, The-Cuong Nguyen, and Céline Bressollette-Bodin. 2022. "Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo" Viruses 14, no. 9: 2077. https://doi.org/10.3390/v14092077

APA Style

McIlroy, D., Peltier, C., Nguyen, M.-L., Manceau, L., Mobuchon, L., Le Baut, N., Nguyen, N.-K., Tran, M.-C., Nguyen, T.-C., & Bressollette-Bodin, C. (2022). Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo. Viruses, 14(9), 2077. https://doi.org/10.3390/v14092077

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