KSHV Epigenetic Regulation

KSHV 表观遗传调控

• 批准号: 10521293
• 负责人: Jae U Jung
• 金额: $ 43.12万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10521293
• 关键词: 3-Dimensional; ATAC-seq; Adopted; Affect; Auxins; Bioinformatics; Blood; Cell Culture Techniques; Cells; ChIP-seq; Chromatin; Chromatin Conformation Capture and Sequencing; Chromatin Loop; Chromatin Structure; Complication; Development; Endothelial Cells; Epigenetic Process; Epithelial Cells; Epithelium; Etiology; Euchromatin; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genomics; Goals; Grant; HIV Infections; Heterochromatin; Histones; Human Herpesvirus 8; Infection; Integration Host Factors; Kaposi Sarcoma; Lead; Lesion; Life Cycle Stages; Lytic; Malignant lymphoid neoplasm; Mediating; Modeling; Mutation; Oral; Palate Kaposi' s Sarcoma; Pattern; Play; Promoter Regions; Regulation; Role; Route; Saliva; Seminal fluid; Site; Structure; Technology; Testing; Tissue Model; Viral; Viral Genes; Virus Replication; cell type; chromosome conformation capture; epigenetic regulation; epigenome; epigenomics; global run on sequencing; histone modification; in vivo; insight; latent infection; lytic gene expression; lytic replication; mutant; next generation sequencing; oral cavity epithelium; oral infection; oral lesion; oral status; oral tissue; particle; programs; single-cell RNA sequencing; three dimensional cell culture; three-dimensional modeling; transcription factor; transcriptomics; transmission process; viral genomics

Project Summary/Abstract While KSHV can be detected in blood and occasionally in semen, it is frequently secreted in saliva which is believed to be the main route of spread. Nearly 25 years after the identification of KSHV, however, the initial steps in KSHV oral infection and the expressions of host and KSHV genes are still poorly understood. Our main question is: while KSHV establishes latency in most cells and KS lesions by default, why does it lead to spontaneous lytic replication in oral epithelial cells and oral lesions? Our hypothesis is: this difference is due to the differences of viral epigenetics and genomics. As the previous grant has been primarily focused on the epigenetic regulation of KSHV, the current study will characterize the high-order genomic organization of KSHV and investigate the transcriptomic and epigenomic regulations of KSHV at the single cell level using 3D organotypic oral tissue infection model that closely resembles in vivo oral transmission.

项目摘要/摘要 虽然KSHV可以在血液中检测到，偶尔也可以在精液中检测到，但它经常在 唾液被认为是主要的传播途径。在鉴定了近25年后 然而，KSHV口腔感染的初始步骤以及宿主和KSHV基因的表达 人们对此仍然知之甚少。我们的主要问题是：虽然KSHV在大多数细胞中建立了潜伏期， KS病变默认情况下，为什么它会导致口腔上皮细胞和口腔中自发的裂解复制 损伤？我们的假设是：这种差异是由于病毒表观遗传学和 基因组学。由于之前的拨款主要集中在KSHV的表观遗传调控上， 目前的研究将表征KSHV的高阶基因组组织，并研究 利用3D器官型口服液在单细胞水平上研究KSHV的转录和表观基因组调控 类似于体内口服传播的组织感染模型。