Regulation of host miRNA activity by Epstein-Barr virus BHRF1

Epstein-Barr 病毒 BHRF1 对宿主 miRNA 活性的调节

• 批准号: 10170258
• 负责人: Rebecca L Skalsky
• 金额: $ 17.6万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-22 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170258
• 关键词: 3' Untranslated Regions; Affect; Antigens; Antineoplastic Agents; Apoptosis; Apoptotic; B-Lymphocytes; BCL2 gene; Binding Sites; Biological Assay; Biological Process; Cell Proliferation; Cell physiology; Cells; Clinical; Code; Complex; DNA Tumor Viruses; Development; Disease; Drug Design; Environment; Epithelial Cells; Epstein-Barr Virus Infections; Epstein-Barr Virus latency; Exhibits; Family member; Gene Expression; Genetic Transcription; Health; Hematologic Neoplasms; Herpesviridae; Homologous Gene; Human; Human Herpesvirus 4; Immune; Immunocompromised Host; In Vitro; Individual; Infection; Knowledge; Lead; Libraries; Life; Life Cycle Stages; Luciferases; Lymphocyte; Lytic; Malignant Neoplasms; Measures; MicroRNAs; Molecular; Monitor; Morbidity - disease rate; Mutation; Northern Blotting; Oncogenic; Pathogenesis; Pilot Projects; Play; Post-Transcriptional Regulation; Process; Production; Proteins; RNA; Regulation; Reporter; Resistance; Role; Shapes; Signal Transduction; Site; Small RNA; Solid Neoplasm; Testing; Transcript; Transplant Recipients; Untranslated RNA; Viral; Viral Proteins; Virus; Virus Diseases; Virus Replication; cellular engineering; experimental study; gene product; genotoxicity; improved; infected B cell; insight; loss of function; member; miRNA expression profiling; mutant; nonhuman primate; novel; recombinant virus; sensor; treatment strategy; vaccine development

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.

microrna是健康和疾病的关键调控因子，影响多种生物过程。许多DNA肿瘤病毒，如eb病毒（EBV）篡夺mirna，在整个感染过程中转录后调节宿主环境和抗原表达。在初步研究中，我们发现了EBV BHRF1基因座表达的转录本之间潜在的新型相互作用，这种相互作用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感染期间的功能作用。通过功能丧失分析，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BHRF1与miR-17/92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BHRF1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BHRF1表达本身如何被控制的基本分子理解，这对疫苗开发至关重要。