Hanna Liimatainen1, Lukas Weseslindtner2, Robert Strassl3, Stephan W Aberle4, Gregor Bond3, Eeva Auvinen5. 1. Department of Virology and Immunology, Helsinki University Hospital Laboratory, Helsinki, Finland; Department of Virology, University of Helsinki, Helsinki, Finland. 2. Department of Virology, University of Helsinki, Helsinki, Finland; Center for Virology, Medical University of Vienna, Vienna, Austria. 3. Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria. 4. Center for Virology, Medical University of Vienna, Vienna, Austria. 5. Department of Virology and Immunology, Helsinki University Hospital Laboratory, Helsinki, Finland; Department of Virology, University of Helsinki, Helsinki, Finland. Electronic address: eeva.auvinen@helsinki.fi.
Abstract
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.
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 PVANpatient 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.
Authors: Jacek Furmaga; Marek Kowalczyk; Tomasz Zapolski; Olga Furmaga; Leszek Krakowski; Grzegorz Rudzki; Andrzej Jaroszyński; Andrzej Jakubczak Journal: Viruses Date: 2021-07-30 Impact factor: 5.048