Regulation of host miRNA activity by Epstein-Barr virus BHRF1

MicroRNAs是健康和疾病中的关键调节因子，影响着多种生物过程。许多DNA肿瘤病毒，如Epstein-Barr病毒(EBV)，在感染过程中利用miRNAs转录后调节宿主环境和抗原表达。在试点研究中，我们发现了EBV BHRF1基因座表达的转录本之间的一种潜在的新的相互作用，它为感染细胞和致癌细胞miR-17/92簇提供了生存优势。在本项目中，我们旨在研究BHRF1和miR-17/92之间的关系，以了解这些相互作用在EBV感染中的功能作用。通过功能丧失分析，我们将确定感染的阶段，在这个阶段，这些相互作用是最关键的。将进行机制研究，以了解BHRF1与miR-17/92以及与其他宿主miRNAs相互作用的分子基础。这些研究将为深入研究BHRF1和其他病毒因子在病毒驱动的癌症背景下如何影响宿主miRNA功能(S)奠定基础，并将提供对BHRF1表达本身如何控制的基本分子理解，这对疫苗开发非常重要。

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.