Abstract

BackgroundBK polyomavirus (BKPyV) infection is a common asymptomatic viral infection in the general population. Severe complications are seen in immunocompromised individuals, such as polyomavirus-associated nephropathy (PyVAN) in renal transplant recipients. Information on BKPyV microRNA expressions is scarce, although polyomavirus-encoded microRNAs have been shown to control viral replication and assist in immune evasion. Whereas the pathogenic role of rearrangements in JC polyomavirus has been well established, little is known about BKPyV rearrangements in PyVAN. ObjectivesTo assess viral microRNA expression and transcriptional control region (TCR) sequence variation in PyVAN patients. Study designbkv-miR-B1-3p and bkv-miR-B1-5p microRNA expression was quantified in 55 plasma samples from 9 PyVAN patients and 2 controls using specific miRNA assays. TCR architectures among the viral populations in each patient were characterized by massive parallel sequencing. Resultsbkv-miR-B1-3p and bkv-miR-B1-5p miRNA expression was established in 85.5% and 98.2% of samples, respectively. On average, an 8.9-fold (bkv-miR-B1-3p) and 8.7-fold (bkv-miR-B1-5p) higher expression levels were detected in PyVAN patients as compared to controls. Rearranged BKPyV strains with duplications and deletions were detected in 7/9 PyVAN patients, but 77.6–99.9% of all sequence reads in all samples represented archetype strains. ConclusionsThe frequent detection and increased expression of miRNAs suggest involvement in PyVAN pathogenesis. Despite the predominance of archetype BKPyV strains, the frequent detection of minor rearranged viral populations urges further study on their role in severe kidney disease. Our results suggest that miRNA expression is increased in PyVAN patients, as well as in the presence of rearranged viral strains.

Highlights

  • BK polyomavirus (BKPyV) infection is a common asymptomatic viral infection in the general population

  • Presumptive polyomavirus-associated nephropathy (PyVAN) diagnosis can be AN made if high BKPyV load in plasma or urine (>104 or >107 copies/mL, respectively) for more than M three weeks is observed [6], but histological examination of allograft biopsy and immunohistochemical SV40 large T antigen staining are used for definitive diagnosis [7]

  • 55 plasma samples were analysed for miRNAs. 5p miRNA expression was established in 54/55 samples (98.2%) with an average Ct value of 39.2, and 3p miRNA in 47/55 samples

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Summary

Introduction

BK polyomavirus (BKPyV) infection is a common asymptomatic viral infection in the general population. Severe complications are seen in immunocompromised individuals, such as polyomavirus-associated nephropathy (PyVAN) in renal transplant recipients. T BKPyV microRNA expressions is scarce, polyomavirus-encoded microRNAs have been IP shown to control viral replication and assist in immune evasion. To assess viral microRNA expression and transcriptional control region (TCR) U sequence variation in PyVAN patients. Bkv-miR-B1-3p and bkv-miR-B1-5p microRNA expression was quantified in 55 M plasma samples from 9 PyVAN patients and 2 controls using specific miRNA assays. In renal C transplant recipients, reactivation of latent BKPyV may cause severe complications [4]. Because up S to 10% of renal transplant recipients develop polyomavirus-associated nephropathy (PyVAN), these U patients are screened for BKPyV viremia and viruria [6].

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