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.

口腔感染代表了人类巨细胞病毒（HCMV）的重要途径 传播。 HCMV感染也是口腔疾病最常见的原因之一 与艾滋病患者有关。了解口腔中HCMV感染的机制 粘膜以及口腔的其他部位将为开发新药提供洞察力 以及治疗和预防HCMV相关的口腔疾病的新型策略。 拟议研究的目的是研究HCMV染色质修饰和 它们在口腔粘膜中的病毒感染中的作用。我们实验室的最新研究表明 在 人类原发性细胞和组织培养物中的HCMV染色质。此外，初步 研究表明，特定的病毒蛋白会影响病毒的表观遗传修饰 染色质，其中一些修饰特异性调节病毒的表达 HCMV生产感染所需的基因表达。 在拟议的研究的最初部分中，我们将筛选出HCMV突变体的集合 删除单个病毒开放式阅读框（ORF）以分离出发生变化的突变体 病毒染色质修饰，并确定对特定重要的病毒决定因素 口服粘膜中HCMV染色质的修饰。然后将进行实验 研究病毒染色质在调节病毒基因中所鉴定的修饰的作用 口腔细胞中的转录和支持病毒感染。此外，实验也将是 进行研究以研究病毒决定因素如何调节特定的HCMV染色质 通过与表观遗传重塑配合物相互作用来修改以促进 口腔中的HCMV感染。这些研究将导致病毒的鉴定 对于HCMV染色质修饰和口腔中病毒感染至关重要的决定因素 粘膜。此外，我们的研究将研究HCMV在口服粘膜和 HCMV编码的决定因素如何调节HCMV染色质修饰和 支持口腔粘膜中的病毒感染。我们的结果将为您提供有关机制的见解 口服粘膜中的HCMV感染，并促进新的治疗策略的发展 以及预防口腔中HCMV的传播以及感染。