BK polyomavirus microRNA expression and sequence variation in polyomavirus-associated nephropathy

https://doi.org/10.1016/j.jcv.2018.02.007Get rights and content
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Highlights

  • BKPyV miRNA expression and TCR sequence variation were analysed in PyVAN patients.

  • Minor rearranged BKPyV populations were frequently detected in most patients.

  • Archetype BKPyV strains were predominant in all patients and seem to associate with PyVAN.

  • miRNAs were frequently detected and expressed at high levels in PyVAN patients.

  • miRNA levels were also elevated in the presence of rearranged viral strains.

Abstract

Background

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. 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.

Objectives

To assess viral microRNA expression and transcriptional control region (TCR) sequence variation in PyVAN patients.

Study design

bkv-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.

Results

bkv-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.

Conclusions

The 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.

Keywords

BKPyV
miRNA
TCR
PyVAN
Rearrangements
Sequence variation

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