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

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.