3-D Oral Mucosa Model for EBV Pathogenesis

EBV 发病机制的 3-D 口腔粘膜模型

• 批准号: 7879677
• 负责人: Raymond Preston Stowe
• 金额: $ 7.75万
• 依托单位: MICROGEN, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-09 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879677
• 关键词: 3-Dimensional; Acquired Immunodeficiency Syndrome; Address; Animal Model; Applications Grants; B-Lymphocytes; Biological Models; Bioreactors; Burkitt Lymphoma; Cell Line; Cells; Coculture Techniques; Complex; Cultured Cells; Desmosomes; Development; EBV-associated disease; Electron Microscopy; Endothelial Cells; Environment; Epithelial; Epstein-Barr Virus Infections; Epstein-Barr pathogenesis; Event; Gene Expression; Goals; HIV; Hairy Leukoplakia; Healthcare Systems; Human; Human Herpesvirus 4; Human body; Immunobiology; Immunologic Surveillance; In Vitro; Individual; Infection; Infectious Mononucleosis; Knowledge; Lateral; Lead; Lesion; Lung; Lymphoma; Lytic; Modeling; Molecular Profiling; Nasopharynx Carcinoma; Oral mucous membrane structure; Pathogenesis; Patients; Research; Research Personnel; Respiratory syncytial virus; Simulate; Staining method; Stains; Structure; System; Tight Junctions; Tissues; Tongue; Tongue Squamous Cell Carcinoma; Viral; Viral Antigens; Viral Genes; Viral Pathogenesis; Virus Replication; cost; experience; flasks; human tissue; immunosuppressed; in vitro Model; in vivo; insight; monolayer; oral cavity epithelium; pathogen; public health relevance

DESCRIPTION (provided by applicant): The goal of this new investigator initiated R03 grant application is to establish a physiologically relevant model of human oral mucosa in order to study the pathogenesis of Epstein-Barr virus (EBV), an important pathogen in AIDS patients. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and other B-lymphocyte lymphomas in immunosuppressed individuals. In addition, lytic EBV replication is associated with oral hairy leukoplakia, a wart-like lesion on the lateral borders of the tongue that develops in a substantial portion of human immunodeficiency virus (HIV)-infected individuals. The mechanisms of primary infection, release, and spread of EBV are poorly understood because there are no suitable in vivo or in vitro oral mucosa model systems to investigate viral pathogenesis under highly controlled conditions. This project undertakes the development of an in vitro model of human oral mucosa using a three-dimensional system in order to study EBV infection of the oral epithelium. The specific aims of the study are: (1) establish a 3-D model of oral mucosa using a heterologous co-culture system, and (2) investigate the infection and replication of EBV in oral mucosa tissue. The establishment of a complex human oral mucosa model will provide new insights into EBV infection of the oral mucosa and lead to a hypothesis-driven R01 grant application addressing EBV immunobiology of the oral epithelium. PUBLIC HEALTH RELEVANCE: Epstein-Barr virus (EBV) EBV is an important pathogen in humans and results in considerable cost to the health care system. EBV is the causative agent of infectious mononucleosis as well as nasopharyngeal carcinoma, Burkitt's lymphoma, and other B-lymphocyte lymphomas in immunosuppressed individuals. In addition, lytic EBV replication is associated with oral hairy leukoplakia, a wart-like lesion on the lateral borders of the tongue that develops in a substantial portion of human immunodeficiency virus (HIV)-infected individuals. The mechanisms of primary infection, release and spread of EBV are poorly understood. Because no in vitro or animal model exists for EBV, critical gaps in knowledge regarding EBV pathogenesis in vivo remain to be answered including how EBV persists in spite of the continuous immune surveillance and what events precede EBV-associated diseases. The establishment of a complex human oral mucosa model will provide new insights into EBV infection of the oral mucosa and lead to hypothesis-driven studies addressing EBV immunobiology of the oral epithelium.

描述（由申请人提供）：该新研究者启动R03授予申请的目的是建立人类口服粘膜上与生理相关的模型，以研究EADS患者的Epstein-Barr病毒（EBV）的发病机理。 EBV是感染性单核细胞增多症以及鼻咽癌，伯基特淋巴瘤和其他B-淋巴细胞淋巴瘤的病因。此外，裂解的EBV复制与口服毛状白细胞相关，这是舌头外侧边界上的疣状病变，在大量人类免疫缺陷病毒（HIV）感染的个体中发育。 EBV原发性感染，释放和扩散的机制知之甚少，因为在高度控制的条件下没有适当的体内或体外口服粘膜模型系统来研究病毒发病机理。该项目采用三维系统来开发人口腔粘膜的体外模型，以研究口服上皮的EBV感染。该研究的具体目的是：（1）使用异源共培养系统建立口服粘膜的3-D模型，以及（2）研究EBV在口腔粘膜组织中的感染和复制。建立复杂的人口腔粘膜模型将为口腔粘膜的EBV感染提供新的见解，并导致假设驱动的R01赠款授予应用，以解决口腔上皮的EBV免疫生物学。 公共卫生相关性：Epstein-Barr病毒（EBV）EBV是人类的重要病原体，其造成了巨大的医疗保健系统。 EBV是感染性单核细胞增多症以及鼻咽癌，伯基特淋巴瘤和其他B-淋巴细胞淋巴瘤的病因。此外，裂解的EBV复制与口服毛状白细胞相关，这是舌头外侧边界上的疣状病变，在大量人类免疫缺陷病毒（HIV）感染的个体中发育。原发性感染，EBV释放和扩散的机制知之甚少。由于不存在EBV的体外或动物模型，因此关于体内EBV发病机理的知识差异仍有待回答，包括尽管有连续的免疫监测以及哪些事件在EBV相关疾病之前，EBV仍在继续。建立复杂的人口腔粘膜模型将为口腔粘膜的EBV感染提供新的见解，并导致以假设驱动的研究来解决口腔上皮的EBV免疫生物学。