Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8200-5. doi: 10.1073/pnas.1301907110. Epub 2013 Apr 29.
Viral microRNAs (miRNAs) play an important role during infection by posttranscriptionally regulating both host and viral gene expression. However, the function of many viral miRNAs remains poorly understood. In this study, we investigated the role of the BK polyomavirus (BKPyV) miRNA in regulating virus replication. The function of the polyomavirus miRNA was investigated in archetype BKPyV, which is the transmissible form of the virus and thought to establish a persistent infection in the host urinary tract. In agreement with previous studies, we show that the BKPyV miRNA targets early mRNAs. Importantly, we show that the miRNA plays a significant role in limiting archetype BKPyV replication in a natural host cell model of infection. This regulation is accomplished through the balance of regulatory elements located within the noncoding control region that control early gene expression and miRNA expression before genome replication. We therefore provide evidence for a unique function of the polyomavirus miRNA that may have important implications for the mechanism of viral persistence.
病毒 microRNAs（miRNAs）在感染过程中通过转录后调控宿主和病毒基因表达发挥着重要作用。然而，许多病毒 miRNAs 的功能仍知之甚少。在这项研究中，我们研究了 BK 多瘤病毒（BKPyV）miRNA 在调节病毒复制中的作用。多瘤病毒 miRNA 的功能是在原型 BKPyV 中研究的，原型 BKPyV 是病毒的可传播形式，被认为在宿主泌尿道中建立持续感染。与先前的研究一致，我们表明 BKPyV miRNA 靶向早期 mRNA。重要的是，我们表明 miRNA 在限制感染的天然宿主细胞模型中的原型 BKPyV 复制中发挥重要作用。这种调节是通过位于非编码控制区的调节元件的平衡来实现的，这些调节元件在基因组复制之前控制早期基因表达和 miRNA 表达。因此，我们为多瘤病毒 miRNA 的独特功能提供了证据，这可能对病毒持续存在的机制具有重要意义。
