Regulation of host miRNA activity by Epstein-Barr virus BHRF1

Epstein-Barr 病毒 BHRF1 对宿主 miRNA 活性的调节

基本信息

批准号：
10039435
负责人：
Rebecca L Skalsky
金额：
$ 22.88万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-22 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10039435
关键词：
3&apos 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

项目摘要

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.

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 Epstein-Barr 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，我们的目标是检查 BHRF1 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。通过功能丧失检测，我们将确定这些相互作用最为关键的感染阶段。将进行机制研究以了解 BHRF1 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 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 表达本身如何控制的基本分子理解，这对于疫苗开发。