Next-generation sequencing shows marked rearrangements of BK polyomavirus that favor but are not required for polyomavirus-associated nephropathy.
BK polyomavirus
NGS
Polyomavirus-Associated nephropathy
TCR
Journal
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
ISSN: 1873-5967
Titre abrégé: J Clin Virol
Pays: Netherlands
ID NLM: 9815671
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
05
08
2019
revised:
18
10
2019
accepted:
11
11
2019
pubmed:
30
11
2019
medline:
7
2
2021
entrez:
30
11
2019
Statut:
ppublish
Résumé
BKPyV is associated with polyomavirus-associated nephropathy (PVAN), a major cause of graft rejection in kidney transplant recipients (KTRs). Mutations occur in the transcriptional control region (TCR) of BKPyV, but whether they are required for the development of PVAN is not completely understood. To this end, we characterized BKPyV TCRs from KTRs to assess whether TCR mutations are associated with PVAN. We analyzed urine and plasma samples of fifteen KTRs with biopsy-confirmed PVAN, presumptive PVAN, or probable PVAN in order to explore the contents of the BKPyV virome. BKPyV TCRs were amplified and deep sequenced to characterize the viral strains. Alterations in block structures and transcription factor binding sites were investigated. The majority of sequences in both urine and plasma samples represented archetype BKPyV TCR. Minor populations harboring rearranged TCRs were detected in all patient groups. In one biopsy-confirmed PVAN patient rearranged TCRs predominated, and in another patient half of all reads represented rearranged sequences. Although archetype BKPyV predominated in most patients, highest proportions and highest numbers of rearranged strains were detected in association with PVAN. TCR mutations seem not necessary for the development of PVAN, but immunosuppression may allow increased viral replication giving rise to TCR variants with enhanced replication efficiency.
Sections du résumé
BACKGROUND
BKPyV is associated with polyomavirus-associated nephropathy (PVAN), a major cause of graft rejection in kidney transplant recipients (KTRs). Mutations occur in the transcriptional control region (TCR) of BKPyV, but whether they are required for the development of PVAN is not completely understood. To this end, we characterized BKPyV TCRs from KTRs to assess whether TCR mutations are associated with PVAN.
STUDY DESIGN
We analyzed urine and plasma samples of fifteen KTRs with biopsy-confirmed PVAN, presumptive PVAN, or probable PVAN in order to explore the contents of the BKPyV virome. BKPyV TCRs were amplified and deep sequenced to characterize the viral strains. Alterations in block structures and transcription factor binding sites were investigated.
RESULTS
The majority of sequences in both urine and plasma samples represented archetype BKPyV TCR. Minor populations harboring rearranged TCRs were detected in all patient groups. In one biopsy-confirmed PVAN patient rearranged TCRs predominated, and in another patient half of all reads represented rearranged sequences.
CONCLUSIONS
Although archetype BKPyV predominated in most patients, highest proportions and highest numbers of rearranged strains were detected in association with PVAN. TCR mutations seem not necessary for the development of PVAN, but immunosuppression may allow increased viral replication giving rise to TCR variants with enhanced replication efficiency.
Identifiants
pubmed: 31783265
pii: S1386-6532(19)30245-8
doi: 10.1016/j.jcv.2019.104215
pii:
doi:
Substances chimiques
DNA, Viral
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104215Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.