Regulation of host miRNA activity by Epstein-Barr virus BHRF1

microRNA是健康和疾病的关键调节因子，影响多种生物过程。许多DNA肿瘤病毒，如EB病毒（EBV）篡夺miRNA转录后调节宿主环境和抗原表达整个感染。在初步研究中，我们发现了EBV BHRF 1基因座表达的转录本之间的潜在新型相互作用，该基因座为感染细胞和致癌细胞miR-17/92簇提供了生存优势。在这个项目中，我们的目标是检查BHRF 1和miR-17/92之间的关系，以了解这些相互作用在EBV感染过程中的功能作用。通过功能丧失试验，我们将确定感染的阶段，其中这些相互作用是最关键的。将进行机制研究以了解BHRF 1与miR-17/92相互作用以及与其他宿主miRNA相互作用的分子基础。这些研究将为深入研究BHRF 1和其他病毒因子如何在病毒驱动的癌症背景下影响宿主miRNA功能奠定基础，并将提供对BHRF 1表达本身如何控制的基本分子理解，这对疫苗开发至关重要。

MicroRNAs are key regulators in health and disease and influence multiple biological processes. Many DNA tumor viruses such as Epstein-Barr virus (EBV) usurp miRNAs to post-transcriptionally regulate the host environment and antigen expression throughout infection. In pilot studies, we have uncovered a potentially novel interaction between transcripts expressed from the EBV BHRF1 locus that provides a survival advantage to infected cells and the oncogenic cellular miR-17/92 cluster. In this project, we aim to examine the relationship between BHRF1 and miR-17/92 in order to understand the functional roles of these interactions during EBV infection. Through loss-of-function assays, we will define the stages of infection whereby these interactions are most critical. Mechanistic studies will be performed to understand the molecular basis of BHRF1 interactions with miR-17/92 as well as interactions with other host miRNAs. These studies will lay the groundwork to examine in depth how BHRF1 and other viral factors impact host miRNA function(s) in the context of virus-driven cancers and will provide an essential molecular understanding of how BHRF1 expression itself is controlled, which is important for vaccine development.