Human cytomegalovirus chromatin modifications in oral infection

口腔感染中的人巨细胞病毒染色质修饰

• 批准号: 8625649
• 负责人: Fenyong Liu
• 金额: $ 39.13万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8625649
• 关键词: AIDS-Related Disorder; Acquired Immunodeficiency Syndrome; Affect; Animal Model; Biological Models; Cell Nucleus; Cells; Chromatin; Chromatin Structure; Collection; Complex; Cytomegalovirus; Cytomegalovirus Infections; DNA-Directed RNA Polymerase; Development; Disease; Early Gene Transcriptions; Epigenetic Process; Exclusion; Exhibits; Gene Deletion; Gene Expression; Genes; Genetic Transcription; Genome; Growth; Herpesviridae; Histones; Human; Immediate-Early Genes; In Vitro; Infection; Laboratories; Late Gene Transcriptions; Lead; Mediating; Methylation; Modeling; Modification; Mouth Diseases; Nucleosomes; Open Reading Frames; Oral; Oral cavity; Oral mucous membrane structure; Patients; Pharmaceutical Preparations; Phase; Polycomb; Post-Translational Protein Processing; Prevention; Proteins; Regulation; Reporting; Research; Role; Route; Staging; System; Tail; Therapeutic Agents; Tissue Model; Tissues; Transcript; Transcription Elongation; Transcriptional Activation; Viral; Viral Genes; Viral Physiology; Viral Proteins; Virus Diseases; Virus Inactivation; chromatin modification; congenital infection; epigenomics; histone modification; insight; keratinocyte; mutant; novel strategies; oral infection; oral tissue; pathogen; promoter; public health relevance; research study; tissue/cell culture; transmission process

Oral infection represents an important route of human cytomegalovirus (HCMV) transmission. HCMV infection is also among the most common causes of oral diseases associated with AIDS patients. Understanding the mechanism of HCMV infection in oral mucosa as well as other parts of the oral cavity will provide insight into developing new drugs and novel strategies for treatment and prevention of HCMV-associated oral diseases. The objective of the proposed research is to study HCMV chromatin modifications and their roles in viral infection in oral mucosa. Recent studies in our laboratory have shown that epigenomic modifications, including histone tail changes by methylation, have been found in HCMV chromatin in human primary oral cell and tissue cultures. Furthermore, preliminary studies have suggested that specific viral proteins affect the epigenetic modifications of viral chromatin, and that some of these modifications specifically modulate the expression of viral gene expression required for HCMV productive infection. In the initial part of the proposed study, we will screen a collection of HCMV mutants with deletion of a single viral open reading frame (ORF) to isolate mutants that exhibit altered viral chromatin modifications and to identify viral determinants important for specific modifications of HCMV chromatin in oral mucosa. Experiments will then be carried out to study the roles of the identified modifications of viral chromatin in regulating viral gene transcription and supporting viral infection in oral cells. Furthermore, experiments will also be carried out to investigate how the viral determinants modulate specific HCMV chromatin modifications by interacting with the epigenetic remodeling complexes in order to facilitate HCMV infection in oral cavity. These studies will lead to the identification of viral determinants important for HCMV chromatin modifications and for viral infection in oral mucosa. Furthermore, our studies will investigate how HCMV replicates in oral mucosa and how HCMV-encoded determinants function to modulate HCMV chromatin modifications and support viral infection in oral mucosa. Our results will provide insight into the mechanism of HCMV infection in oral mucosa and facilitate the development of novel strategies for treatment and prevention of the transmission as well as infection of HCMV in oral cavity.

口腔感染是人巨细胞病毒（HCMV）感染的重要途径 传输HCMV感染也是口腔疾病的最常见原因之一 与艾滋病患者有关。口腔巨细胞病毒感染机制的探讨 粘膜以及口腔的其他部分将为开发新药物提供见解 以及治疗和预防HCMV相关口腔疾病的新策略。 这项研究的目的是研究HCMV染色质修饰， 它们在口腔粘膜病毒感染中的作用。我们实验室最近的研究表明， 表观基因组修饰，包括甲基化引起的组蛋白尾部变化，已经在 人口腔原代细胞和组织培养中的HCMV染色质。此外，初步 研究表明，特定的病毒蛋白影响病毒的表观遗传修饰， 这些修饰中的一些特异性地调节病毒的表达， HCMV生产性感染所需的基因表达 在本研究的初始阶段，我们将筛选一系列HCMV突变体， 通过缺失单个病毒开放阅读框（ORF）来分离突变体， 病毒染色质修饰，并确定病毒决定簇的重要性， 口腔粘膜中HCMV染色质的修饰。然后将进行实验， 研究已鉴定的病毒染色质修饰在调节病毒基因中的作用 转录和支持口腔细胞中的病毒感染。此外，实验还将 研究病毒决定簇如何调节特异性HCMV染色质 通过与表观遗传重塑复合物相互作用进行修饰，以促进 口腔HCMV感染。这些研究将导致病毒的鉴定 口腔中HCMV染色质修饰和病毒感染的重要决定因素 粘膜此外，我们的研究将探讨HCMV如何在口腔粘膜中复制， HCMV编码的决定簇如何调节HCMV染色质修饰， 支持口腔粘膜中病毒感染。我们的研究结果将提供深入了解的机制 口腔粘膜中HCMV感染并促进新治疗策略的发展 预防HCMV在口腔内的传播和感染。