Abstract
BackgroundPolyomavirus BK (BKV) encodes two mature miRNAs that regulate the viral life cycle. ObjectivesThis study investigated the autoregulatory and immunomodulatory effects of these miRNAs that have been defined in culture systems, but subject to only limited exploration in clinical samples. MethodsBKV-miR-B1-5p, BKV-miR-BJ1-3p, BKV DNA and BKV VP-1 mRNA levels were measured in 32 paired obtained plasma & urine samples from kidney transplant patients with (a) early stage infection manifesting as viruria, and (b) later stage infections complicated by viremia. ResultsAll patients showed abundant urine miRNAs (7.84E + 02-1.91E + 06 copies/ml, but plasma miRNA was below the limit of detection. There was no statistically significant difference in urinary miRNA levels between viruric and viremic patients. Median 5p miRNA load was 4–6 logs lower than the BKV genomic load. Higher miRNA levels in the urine were associated not with lower but higher urinary viral loads. BKV preferentially used the 3p miRNA for its interactions with host cell mRNAs. The mean ratio of 5p/3p in patients with viruria was 0.09, and 0.03 in patients with viremia. ConclusionsThe data suggest that immune evasion functions of BKV miRNAs over-ride the negative autoregulatory feedback effects in kidney transplant patients with active viral replication.
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