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      Longitudinal monitoring of BKPyV miRNA levels in kidney transplant recipients with BKPyV‐related pathology reflects viral DNA levels and remain high in viremia patients after clearance of viral DNA

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          Abstract

          Introduction

          It is unclear whether polyomavirus BK (BKPyV) microribonucleic acid (miRNA) measurement has additional diagnostic and predictive value in kidney transplant recipients (KTR) as compared to current methods of monitoring BKPyV DNA loads.

          Patients and methods

          A retrospective, longitudinal study was performed in 30 KTR with BKPyV viruria ( n = 10), BKPyV viremia ( n = 10), or BKPyV‐associated neuropathy (BKPyVAN) ( n = 10). Bkv‐miR‐B1‐3p and 5p and BKPyV DNA load were measured in urine and plasma and compared using receiver operating characteristic (ROC) curves.

          Results

          Levels of Bkv‐miR‐B1‐3p and 5p and BKPyV DNA correlated strongly. Overall, mostly analog courses of urinary and plasma miRNA and DNA loads were observed. Areas under the ROC curves were not significantly different between miRNAs and DNA. Only, in contrast to BKPyV DNA load, BKPyV miRNA levels increased from 6 to 12 months in the viremia group, while in the BKPyVAN group, a decline was seen in both DNA and miRNA.

          Conclusions

          In this study, we could not demonstrate an additional value of BKPyV miRNA detection compared to BKPyV DNA monitoring in the early phase after kidney transplantation. We did observe significant differences between the viremia and the BKPyVAN groups during follow‐up. This study was performed with a small number of patients and therefore results should be verified in a larger patient cohort. Furthermore, future studies with larger patient groups are necessary to elucidate final clinical value of these data.

          Abstract

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          Most cited references21

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          Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach

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            Many roads to maturity: microRNA biogenesis pathways and their regulation.

            MicroRNAs are important regulators of gene expression that control both physiological and pathological processes such as development and cancer. Although their mode of action has attracted great attention, the principles governing their expression and activity are only beginning to emerge. Recent studies have introduced a paradigm shift in our understanding of the microRNA biogenesis pathway, which was previously believed to be universal to all microRNAs. Maturation steps specific to individual microRNAs have been uncovered, and these offer a plethora of regulatory options after transcription with multiple proteins affecting microRNA processing efficiency. Here we review the recent advances in knowledge of the microRNA biosynthesis pathways and discuss their impact on post-transcriptional microRNA regulation during tumour development.
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              MicroRNAs as mediators of viral evasion of the immune system.

              Cellular microRNAs serve key roles in the post-transcriptional regulation of almost every cellular gene-regulatory pathway, and it therefore is not surprising that viruses have found ways to subvert this process. Several viruses encode microRNAs that directly downregulate the expression of factors of the innate immune system, including proteins involved in promoting apoptosis and recruiting effector cells of the immune system. Viruses have also evolved the ability to downregulate or upregulate the expression of specific cellular miRNAs to enhance their replication. This Review provides an overview of the present knowledge of the complex interactions of viruses with the microRNA machinery of cells.
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                Author and article information

                Contributors
                w.b.van.doesum@umcg.nl
                Journal
                Transpl Infect Dis
                Transpl Infect Dis
                10.1111/(ISSN)1399-3062
                TID
                Transplant Infectious Disease
                John Wiley and Sons Inc. (Hoboken )
                1398-2273
                1399-3062
                12 August 2022
                December 2022
                : 24
                : 6 ( doiID: 10.1111/tid.v24.6 )
                : e13927
                Affiliations
                [ 1 ] Department of Internal Medicine, Division of Nephrology University of Groningen, University Medical Center Groningen Groningen The Netherlands
                [ 2 ] Department of Medical Microbiology University of Groningen, University Medical Center Groningen Groningen The Netherlands
                [ 3 ] Department of Pathology & Medical Biology Division of Pathology University of Groningen, University Medical Center Groningen Groningen The Netherlands
                [ 4 ] Department of Epidemiology University of Groningen, University Medical Center Groningen Groningen The Netherlands
                [ 5 ] Department of Medical Microbiology University of Utrecht University Medical Center Utrecht Utrecht The Netherlands
                Author notes
                [*] [* ] Correspondence

                Willem B. van Doesum, Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

                Email: w.b.van.doesum@ 123456umcg.nl

                Author information
                https://orcid.org/0000-0002-9714-1357
                https://orcid.org/0000-0001-9182-8986
                Article
                TID13927
                10.1111/tid.13927
                10077896
                35916729
                bcf2c5bf-66c3-47a6-af17-1b9f879ce4ed
                © 2022 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 14 June 2022
                : 05 February 2022
                : 27 June 2022
                Page count
                Figures: 6, Tables: 1, Pages: 8, Words: 5222
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                December 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:06.04.2023

                Transplantation
                bk virus nephropathy,bkpyv,kidney transplantation,longitudinal,marker,mirna
                Transplantation
                bk virus nephropathy, bkpyv, kidney transplantation, longitudinal, marker, mirna

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