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: 8734379
• 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/8734379
• 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

DESCRIPTION (provided by applicant): 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.

DESCRIPTION (provided by applicant): 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.了解口腔粘膜中HCMV感染的机制以及口腔的其他部位，将为开发新药和新型药物的治疗和预防HCMV相关的口腔疾病提供洞察力。 The objective of the proposed research is to study HCMV chromatin modifications and their roles in viral infection in oral mucosa.我们实验室中的最新研究表明，在人类原发性口腔细胞和组织培养物中的HCMV染色质中发现了表观基因组修饰，包括组蛋白的尾巴变化。 Furthermore, preliminary studies have suggested that specific viral proteins affect the epigenetic modifications 病毒染色质，其中一些修饰特异性调节了HCMV生产感染所需的病毒基因表达的表达。 在拟议的研究的最初部分中，我们将筛选出具有单个病毒开放式阅读框（ORF）的HCMV突变体的集合，以分离出表现出改变病毒染色质修饰的变化的突变体，并鉴定出对口服Mucosa中HCMV染色质的特定修饰重要的病毒决定因素。然后将进行实验，以研究病毒染色质在调节病毒基因转录和支持口腔细胞中的病毒感染中鉴定的修饰的作用。此外，还将进行实验，以研究病毒决定因素如何通过与表观遗传重塑复合物相互作用来调节特定的HCMV染色质修饰，以促进口腔中的HCMV感染。这些研究将导致鉴定对HCMV染色质修饰和口服粘膜病毒感染重要的病毒决定因素。此外，我们的研究将研究HCMV如何在口服粘膜中复制以及HCMV编码的决定因素如何调节HCMV染色质修饰并支持口服粘膜中的病毒感染。 Our results will provide insight into the 口腔粘膜中HCMV感染的机制，并促进了口腔中HCMV的治疗和预防疾病的新型策略。