Project 3 - Characterizing the Amplification Factories of Epstein-Barr Virus and Kaposi's Sarcoma-associated Herpesvirus

项目 3 - 描述 Epstein-Barr 病毒和卡波西肉瘤相关疱疹病毒的扩增工厂

基本信息

批准号：
10910337
负责人：
WILLIAM M. SUGDEN
金额：
$ 11.46万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10910337
关键词：
Antiviral Therapy Architecture Binding Carcinoma Cell Nucleus Cells Chromatin Coupled DNA DNA Repair Gene DNA biosynthesis DNA-Directed DNA Polymerase Equipment Exclusion Fluorescence Microscopy Funding Gene Expression Regulation Genes Genetic Transcription Genome Herpesviridae Histones Human Human Genetics Human Herpesvirus 4 Human Herpesvirus 8 Infection prevention Late Gene Transcriptions Learning Life Life Cycle Stages Lymphoma Lytic Phase Malignant Neoplasms Mediating Microscopy Molecular Biology Molecular Chaperones Molecular Genetics Nuclear Nuclear Envelope Nucleocapsid Oncogenic Viruses Persons Phase Plasmids Process Productivity Property Proteins Site Source Statistical Data Interpretation Structural Protein Structure Transcript Transmission Electron Microscopy Viral Viral Genes Viral Proteins Virus Virus Replication Visualization Work light microscopy live cell imaging new technology recruit sarcoma transcription factor transmission process tumor vaccine access viral DNA

项目摘要

PROJECT 3 − SUMMARY/ABSTRACT Epstein-Barr Virus (EBV) and Kaposi's Sarcoma Herpesvirus (KSHV) cause lymphomas, carcinomas, and sarcomas in people across the world. No specific anti-viral therapies or vaccines are available now to treat these tumors or to prevent infections with EBV or KSHV. During the current funding period, we have developed new technologies and used them to uncover exciting discoveries about entry into and progression through the productive or lytic phase of the life-cycle of EBV. We have developed live-cell imaging of intact, infectious genomes of EBV and KSHV and found that during its lytic cycle EBV amplifies its DNA in discrete sites or factories, mediates a dramatic concentration of cellular chromatin at the nuclear periphery, and inhibits synthesis of histone chaperones. We have also found that this amplified viral DNA lacks histones and is the template for viral late gene transcription. We shall examine at the single cell level the formation of both EBV's and KSHV's amplification factories, their consolidation of cellular chromatin, and their mechanisms of transcription of viral late genes in these factories. These detailed studies will identify virus-specific processes that can be targeted to block virus spread.

项目 3 – 摘要/摘要 EB 病毒 (EBV) 和卡波西肉瘤疱疹病毒 (KSHV) 可引起淋巴瘤、癌和目前尚无特定的抗病毒疗法或疫苗可用于治疗世界各地的肉瘤。这些肿瘤或预防 EBV 或 KSHV 感染在当前资助期间，我们有。开发新技术并利用它们来发现有关进入和进步的令人兴奋的发现我们开发了完整、完整的活细胞成像。研究人员对 EBV 和 KSHV 的感染性基因组进行了研究，发现在其裂解周期中 EBV 以离散的方式扩增其 DNA 位点或工厂，介导细胞核外围的细胞染色质的显着浓度，并抑制我们还发现这种扩增的病毒 DNA 缺乏组蛋白，并且是组蛋白伴侣的合成。我们将在单细胞水平上检查两种 EBV 的形成。和 KSHV 的扩增、细胞染色质的巩固及其机制这些详细的研究将确定病毒特定的过程。可以有针对性地阻止病毒传播。