Human cytomegalovirus chromatin modifications in oral infection

描述（由申请人提供）：口腔感染是人类巨细胞病毒（HCMV）传播的重要途径。HCMV感染也是与艾滋病患者相关的口腔疾病的最常见原因之一。了解HCMV感染口腔黏膜及口腔其他部位的机制，将为开发治疗和预防HCMV相关口腔疾病的新药和新策略提供见解。本研究的目的是研究HCMV染色质修饰及其在口腔黏膜病毒感染中的作用。我们实验室最近的研究表明，在人原代口腔细胞和组织培养的HCMV染色质中发现了表观基因组修饰，包括甲基化引起的组蛋白尾部变化。此外，初步研究表明，特定的病毒蛋白影响表观遗传修饰

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.