Human cytomegalovirus chromatin modifications in oral infection

口腔感染是人类巨细胞病毒感染的重要途径 变速箱。人巨细胞病毒感染也是口腔疾病最常见的原因之一。 与艾滋病患者有关。人巨细胞病毒口腔感染机制的研究 粘膜和口腔的其他部分将为开发新药提供洞察力。 以及治疗和预防巨细胞病毒相关口腔疾病的新策略。 拟议研究的目的是研究人巨细胞病毒染色质的修饰和 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，已在 人口腔原代细胞和组织培养中的人巨细胞病毒染色质。此外，初步的 研究表明，特定的病毒蛋白影响病毒的表观遗传修饰 染色质，并且这些修饰中的一些特定地调节病毒的表达 人巨细胞病毒生产性感染所需的基因表达。 在拟议研究的初始部分，我们将筛选一组hcmv突变体。 通过删除单个病毒开放阅读框架(ORF)来分离表现出改变的突变体 病毒染色质修饰和识别病毒决定簇 口腔粘膜中人巨细胞病毒染色质的修饰然后将进行实验，以 病毒染色质修饰在病毒基因调控中的作用研究 转录和支持口腔细胞中的病毒感染。此外，实验也将被 研究病毒决定簇如何调节特定的人巨细胞病毒染色质 通过与表观重塑复合体相互作用进行修饰，以促进 口腔内人巨细胞病毒感染。这些研究将导致病毒的鉴定 HCMV染色质修饰和口腔病毒感染的重要决定因素 粘膜。此外，我们的研究将调查巨细胞病毒如何在口腔粘膜和 人巨细胞病毒编码的决定簇如何调节人巨细胞病毒染色质修饰和 支持口腔粘膜中的病毒感染。我们的研究结果将为我们深入了解 口腔粘膜中人巨细胞病毒感染并促进新的治疗策略的发展 预防巨细胞病毒在口腔内的传播和感染。

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.