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.

项目概要/摘要 虽然 KSHV 可以在血液中检测到，偶尔在精液中检测到，但它经常分泌于 唾液被认为是主要传播途径。在确认身份后近 25 年 然而，KSHV 口腔感染的初始步骤以及宿主和 KSHV 基因的表达 仍然知之甚少。我们的主要问题是：虽然 KSHV 在大多数单元中建立了延迟，并且 默认为KS病变，为何会导致口腔上皮细胞和口腔黏膜自发裂解复制 病变？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。由于之前的资助主要集中在 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调查 使用 3D 器官型口腔在单细胞水平上对 KSHV 进行转录组和表观基因组调控 与体内口腔传播非常相似的组织感染模型。