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30 Bd Jean Monnet

Discipline(s) enseignée(s)

Virologie (L3, M1), Microbiologie Générale (L2), Mécanismes d'Evolution (L1)

Thèmes de recherche

Neutralizing antibody response to BK polyomavirus (BKPyV); evolution of the BKPyV capsid.

use of labeled BKPyV VLPs to obtain broadly neutralizing antibodies in ANR-17-CE17-0003
With respect to antibodies, in the context of the ANR BKNAB project, Ngoc-Khanh Nguyen (PhD co-directed with X. Saulquin CRCINA, defended 31/3/2021) was able to sort BKPyV-specific B-cells using labeled BKPyV capsids, and analyze their antibody repertoire by 10xGenomics single-cell RNASeq. This allowed us to generate several neutralizing monoclonal antibodies against the virus.
Data from this project was presented in oral communications at national (AFIPP 2019, SFI 2021) and international (IUMS 2020) scientific meetings.

VP1 gI mutant structures

In kidney transplant recipients with persistent BKPyV replication, we found that mutations in the capsid can allow the virus to escape from the host antibody response, and also modify the tropism of the virus. Recently, Marie Sorin (PhD co-directed with Thilo Stehle, Tubingen University) obtained the crystal structures of several of these mutants, including one variant that does not bind to any known BKPyV receptor, but is nevertheless infectious.
Data presented in oral communications at AFIPP 2021.

MutPatterns Analysis
To understand how mutations arise in the virus genome, Nicolas Le Baut (Master 1 project, 2021) analyzed NGS data from patient samples to identify patterns in the types of mutations that arise in the VP1 gene. This confirmed that editing by the host APOBEC proteins is a major driver of virus genome mutation, and we also identified a separate mutation signature, suggesting that at least one other biological process contributes to the genetic variability of BKPyV.


Informations complémentaires

Recent publications:

Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo.
McIlroy D, Peltier C, Nguyen ML, Manceau L, Mobuchon L, Le Baut N, Nguyen NK, Tran MC, Nguyen TC, Bressollette-Bodin C.
Viruses. 2022 Sep 19;14(9):2077. doi: 10.3390/v14092077.
PMID: 36146883 

The humoral response to BK polyomavirus in kidney transplant recipients is dominated by IgM antibodies that use a distinct repertoire compared to IgG against the same antigen
Nguyen Ngoc-Khanh, Gautreau-Rolland Laetitia, Devilder Marie-Claire, Fourgeux Cynthia, Sinha Debajyoti, Poschmann Jeremie, Hourmant Maryvonne, Bressollette-Bodin Céline, Saulquin Xavier, McIlroy Dorian

Persistent BK Polyomavirus Viruria is Associated with Accumulation of VP1 Mutations and Neutralization Escape.
McIlroy D, Hönemann M, Nguyen NK, Barbier P, Peltier C, Rodallec A, Halary F, Przyrowski E, Liebert U, Hourmant M, Bressollette-Bodin C.
Viruses. 2020 Jul 29;12(8):824. doi: 10.3390/v12080824.PMID: 32751274

Intra-patient viral evolution in polyomavirus-related diseases.
McIlroy D, Halary F, Bressollette-Bodin C.Philos Trans R Soc Lond B Biol Sci. 2019 May 27;374(1773):20180301. doi: 10.1098/rstb.2018.0301.PMID: 30955497