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Updated: Feb 13, 2026
Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry
Published on: July 13, 2019
BK polyomavirus microRNA expression and sequence variation in polyomavirus-associated nephropathy
Elina Virtanen1, Hanna Seppälä1, Ilkka Helanterä2
1Department of Virology, Helsinki University Hospital Laboratory and University of Helsinki, 00014 Helsinki, Finland.
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.
Insights
BK polyomavirus (BKPyV) infection can cause severe kidney disease (PyVAN) in transplant patients. This study found increased BKPyV microRNA expression and rearranged viral strains in PyVAN patients, suggesting their role in disease development.
Area of Science:
- Virology
- Immunology
- Nephrology
Background:
- BK polyomavirus (BKPyV) is a common virus, but can cause severe complications like polyomavirus-associated nephropathy (PyVAN) in immunocompromised individuals, particularly renal transplant recipients.
- While polyomavirus microRNAs are known to regulate viral replication and immune evasion, information on BKPyV microRNA expression in PyVAN is limited.
- The role of BKPyV rearrangements in PyVAN pathogenesis is largely unknown, contrasting with the established role of JC polyomavirus rearrangements.
Purpose of the Study:
- To investigate the expression of BKPyV-encoded microRNAs (bkv-miR-B1-3p and bkv-miR-B1-5p) in patients with PyVAN.
- To analyze the sequence variation and architecture of the transcriptional control region (TCR) of BKPyV in PyVAN patients.
- To determine the potential association between microRNA expression, viral rearrangements, and the development of PyVAN.
Main Methods:
- Quantification of bkv-miR-B1-3p and bkv-miR-B1-5p expression in plasma samples from PyVAN patients and controls using specific miRNA assays.
- Massive parallel sequencing was employed to characterize the TCR architectures within the BKPyV populations in each patient.
- Analysis included comparison of microRNA expression levels and the prevalence of rearranged viral strains between PyVAN patients and healthy controls.
Main Results:
- Both bkv-miR-B1-3p and bkv-miR-B1-5p were detected in a high percentage of samples (85.5% and 98.2%, respectively).
- PyVAN patients exhibited significantly higher expression levels of both microRNAs (8.9-fold for bkv-miR-B1-3p and 8.7-fold for bkv-miR-B1-5p) compared to controls.
- Rearranged BKPyV strains, characterized by duplications and deletions, were identified in 7 out of 9 PyVAN patients, although archetype strains predominated (77.6-99.9% of reads).
Conclusions:
- The frequent detection and elevated expression of BKPyV microRNAs suggest their involvement in the pathogenesis of PyVAN.
- The presence of minor rearranged BKPyV populations, despite the dominance of archetype strains, warrants further investigation into their role in severe kidney disease.
- Increased microRNA expression and the presence of rearranged viral strains are associated with PyVAN in renal transplant recipients.
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