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: 8974718
• 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/8974718
• 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; Human; In Vitro; Infection; Laboratories; Lead; Modeling; Mouth Diseases; Myelogenous; Open Reading Frames; Oral; Oral cavity; Oral mucous membrane structure; Pathogenesis; 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 Proteins; Virus Diseases; congenital infection; insight; keratinocyte; latent persistent infection; monocyte; mutant; novel strategies; oral infection; oral tissue; particle; pathogen; public health relevance; research study; tissue/cell culture; transmission process

 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（由适用提供）：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。 HCMV的持续性和潜在感染在口腔中很常见。 HCMV的口服储量在病毒传播和发病机理中起重要作用。例如，口服粘膜中的HCMV感染，该感染既可以控制但持续的产生和脱落感染性颗粒，而没有明显的口腔疾病发作，这代表了病毒传播的主要来源。了解口腔粘膜中HCMV感染的机制以及口腔的其他部分，并从其口腔储备中消除HCMV是预防HCMV传播及其相关疾病的核心。拟议的研究的目的是研究口腔粘膜中的HCMV持续感染。我们最近表明，HCMV感染可以参与受到约束和控制的病毒后代的产生，并且在培养的口腔细胞和组织中没有显着的细胞质效应，这表明这些培养的​​细胞和组织可以用作研究HCMV在口腔粘膜中的HCMV生产性和持久性感染的模型。此外，初步研究表明，特定的病毒蛋白阻止凋亡并调节病毒基因转录，从而导致感染细胞的保护和存活 在口腔粘膜中建立受控但持续的感染。在提议研究的最初部分中，我们将筛选出单个病毒开放阅读框（ORF）缺失的HCMV突变体的集合，以鉴定对口腔粘膜中病毒生产和持续性感染重要的病毒决定剂。然后将进行实验以研究已识别的作用 支持口腔细胞病毒感染的病毒因素。此外，还将进行实验以研究病毒如何确定调节病毒基因转录并抑制 病毒诱导的凋亡通过与宿主转录机制和细胞凋亡过程的成分相互作用，以实现口腔中成功的HCMV持续感染。这些研究将导致对口腔粘膜中Vira感染重要的病毒决定剂的鉴定。我们的结果还将洞悉口腔粘膜中HCMV生产性和持续感染的机制，并支持开发新的策略，以消除其口腔储层中消除HCMV感染的新策略，并预防口腔腔中HCMV的传播和感染。