BACKGROUND Polyomavirus BK (BKV) encodes two mature miRNAs that regulate the viral life cycle. OBJECTIVES This 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. METHODS BKV-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. RESULTS All 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. CONCLUSIONS The data suggest that immune evasion functions of BKV miRNAs over-ride the negative autoregulatory feedback effects in kidney transplant patients with active viral replication.

中文翻译：

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肾移植患者中BKV编码的成熟MicroRNA的检测：临床和生物学见解。

背景技术多瘤病毒BK（BKV）编码两个成熟的miRNA，它们调节病毒的生命周期。目的本研究调查了在培养系统中已定义但仅在临床样品中进行有限探索的这些miRNA的自调节和免疫调节作用。方法对32例肾移植患者的血浆和尿液配对样本中的BKV-miR-B1-5p，BKV-miR-BJ1-3p，BKV DNA和BKV VP-1 mRNA水平进行测定（a）早期感染表现为病毒血症。 （b）后期感染并发病毒血症。结果所有患者均显示丰富的尿中miRNA（7.84E + 02-1.91E + 06拷贝/ ml，但血浆miRNA低于检测限，病毒性和病毒血症性患者的尿中miRNA水平无统计学意义。中位5p miRNA负载比BKV基因组负载低4-6个对数。尿液中较高的miRNA水平与较低但较高的尿液病毒载量无关。BKV优先使用3p miRNA与宿主细胞mRNA相互作用。病毒血症患者的5p / 3p的平均比率为0.09，病毒血症患者的平均比率为0.03。结论数据表明，在活动性病毒复制的肾脏移植患者中，BKV miRNA的免疫逃逸功能优于负的自动调节反馈作用。