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.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with several cancers. Despite clinical advances, EBV continues to be a significant cause of morbidity in individuals with immune deficiencies and can be life-threatening for transplant patients. The proposed study will specifically examine how the anti-apoptotic EBV BHRF1 locus interacts with and impacts activity of oncogenic host microRNAs. Understanding how viral factors regulate cellular processes at the molecular level can lead to improved drug design and new treatment strategies for viral disease.
