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: 8105314
• 负责人: Raymond Preston Stowe
• 金额: $ 7.67万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8105314
• 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）：这位新研究者发起的 R03 拨款申请的目标是建立人类口腔粘膜的生理相关模型，以研究艾滋病患者的重要病原体 Epstein-Barr 病毒（EBV）的发病机制。 EBV 是免疫抑制个体中传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原体。此外，裂解性 EBV 复制与口腔毛状白斑有关，口腔毛状白斑是一种舌头外侧边缘的疣状病变，在大部分人类免疫缺陷病毒 (HIV) 感染者中都会出现。由于没有合适的体内或体外口腔粘膜模型系统来研究高度控制条件下的病毒发病机制，因此对 EBV 的原发感染、释放和传播机制知之甚少。该项目利用三维系统开发人类口腔粘膜的体外模型，以研究口腔上皮的 EBV 感染。该研究的具体目的是：（1）利用异源共培养系统建立口腔粘膜3D模型，（2）研究EBV在口腔粘膜组织中的感染和复制。复杂的人类口腔粘膜模型的建立将为口腔粘膜 EBV 感染提供新的见解，并导致以假设为驱动的 R01 拨款申请，解决口腔上皮的 EBV 免疫生物学问题。 公共卫生相关性：EB 病毒 (EBV) EBV 是人类的一种重要病原体，会给医疗保健系统带来相当大的成本。 EBV 是免疫抑制个体中传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原体。此外，裂解性 EBV 复制与口腔毛状白斑有关，口腔毛状白斑是一种舌头外侧边缘的疣状病变，在大部分人类免疫缺陷病毒 (HIV) 感染者中都会出现。 EB 病毒的原发感染、释放和传播机制尚不清楚。由于不存在 EBV 的体外或动物模型，有关 EBV 体内发病机制的关键知识空白仍有待解答，包括 EBV 在持续免疫监视下如何持续存在以及 EBV 相关疾病发生之前发生的事件。复杂的人类口腔粘膜模型的建立将为口腔粘膜 EBV 感染提供新的见解，并引发针对口腔上皮 EBV 免疫生物学的假设驱动研究。