Persistent infection of human cytomegalovirus in oral mucosa

口腔粘膜持续感染人巨细胞病毒

• 批准号: 9108375
• 负责人: Fenyong Liu
• 金额: $ 38.33万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-10 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9108375
• 关键词: AIDS-Related Disorder; Acquired Immunodeficiency Syndrome; Animal Model; Antiviral Agents; Apoptosis; Apoptotic; Biological Models; Cells; Cessation of life; Collection; Cytomegalovirus; Cytomegalovirus Infections; Development; Disease; Early Gene Transcriptions; Exhibits; Gene Deletion; Genes; Genetic Transcription; Growth; Health; Human; In Vitro; Infection; Laboratories; Lead; Modeling; Mouth Diseases; Myelogenous; Open Reading Frames; Oral; Oral cavity; Oral mucous membrane structure; Pathway interactions; Patients; Play; Prevention; Process; Production; Proteins; Reporting; Research; Role; Salivary Glands; Small Interfering RNA; Source; Stem cells; System; Therapeutic Agents; Tissue Model; Tissues; Transcript; Viral; Viral Genes; Viral Pathogenesis; Viral Proteins; Virus Diseases; Virus Replication; congenital infection; insight; keratinocyte; latent persistent infection; monocyte; mutant; novel strategies; oral infection; oral tissue; overexpression; particle; pathogen; research study; tissue/cell culture; transmission process; viral transmission

 DESCRIPTION (provided by applicant): Human cytomegalovirus (HCMV) is among the most common causes of oral diseases associated with AIDS patients. Persistent and latent infections of HCMV are common in oral cavity. Oral reservoirs of HCMV play an important role in viral transmission and pathogenesis. For example, HCMV infection in oral mucosa, which engages controlled but persistent production and shedding of infectious particles without apparent onset of oral diseases, represents the major source for viral transmission. Understanding the mechanism of HCMV infection in oral mucosa as well as other parts of the oral cavity and eliminating HCMV from its oral reservoirs are central to the prevention of HCMV transmission and its associated diseases. The objective of the proposed research is to study HCMV persistent infection in oral mucosa. We have recently showed that HCMV infection can engage a restrained and controlled production of viral progeny and exhibit no significant cytopathic effect in cultured oral cells and tissues, suggesting that these cultured cells and tissues can be used as the models to study HCMV productive and persistent infections in oral mucosa. Furthermore, preliminary studies have suggested that specific viral proteins block apoptosis and modulate viral gene transcription, leading to the protection and survival of the infected cells and the establishment of controlled but persistent infection in oral mucosa. In the initial part of th proposed study, we will screen a collection of HCMV mutants with deletion of a single viral open reading frame (ORF) to identify viral determinants important for viral productive and persistent infection in oral mucosa. Experiments will then be carried out to study the roles of the identified viral factors in supporting viral infection in oral cells. Furthermore, experiments will also be carried out to investigate how the viral determinants modulate viral gene transcription and inhibit viral-induced apoptosis by interacting with the host transcription machinery and the components of the cellular apoptotic processes in order to achieve successful HCMV persistent infection in oral cavity. These studies will lead to the identification of viral determinants important for vira infection in oral mucosa. Our results will also provide insight into the mechanism of HCMV productive and persistent infection in oral mucosa and facilitate the development of novel strategies for eliminating HCMV infection from its oral reservoirs and for prevention of the transmission and infection of HCMV in oral cavity.

 描述(申请人提供)：人类巨细胞病毒(HCMV)是与艾滋病患者相关的口腔疾病的最常见原因之一。口腔内人巨细胞病毒持续感染和潜伏感染较为常见。口腔型巨细胞病毒在病毒传播和致病机制中起着重要作用。例如，口腔粘膜中的巨细胞病毒感染是病毒传播的主要来源，它可控制但持续地产生和脱落感染性颗粒，而不会出现明显的口腔疾病。了解人巨细胞病毒在口腔粘膜及口腔其他部位的感染机制，清除口腔内的人巨细胞病毒，是预防巨细胞病毒传播及相关疾病的关键。本研究的目的是研究口腔粘膜中人巨细胞病毒的持续感染情况。我们最近发现，在培养的口腔细胞和组织中，HCMV感染可以抑制和控制病毒后代的产生，并且没有表现出明显的细胞病变效应，这表明这些培养的细胞和组织可以作为研究口腔粘膜中HCMV产生性和持续性感染的模型。此外，初步研究表明，特定的病毒蛋白阻止细胞凋亡并调节病毒基因转录，从而保护受感染的细胞并使其存活。 口腔黏膜可控但持续感染模型的建立。在这项拟议的研究的初始部分，我们将筛选一组缺失单个病毒开放阅读框架(ORF)的HCMV突变株，以确定对口腔粘膜中病毒产生和持续感染至关重要的病毒决定因素。然后将进行实验，以研究已识别的 支持口腔细胞中病毒感染的病毒因素。此外，还将进行实验，以研究病毒决定因素如何调节病毒基因转录和抑制 病毒通过与宿主转录机制和细胞凋亡过程的组成部分相互作用来诱导细胞凋亡，从而实现成功的口腔内HCMV持续感染。这些研究将导致确定对口腔粘膜中病毒感染重要的病毒决定因素。我们的研究结果也将有助于深入了解巨细胞病毒在口腔粘膜中产生和持续感染的机制，并有助于开发新的策略来消除其口腔蓄水池中的巨细胞病毒感染，防止巨细胞病毒在口腔内的传播和感染。