Exploring roles of protein deamidation in oral inflammation

探索蛋白质脱酰胺在口腔炎症中的作用

• 批准号: 9752511
• 负责人: Pinghui Feng
• 金额: $ 104.23万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9752511
• 关键词: Address; Anatomy; Cells; Chronic; Clinical Research; Cytomegalovirus; Disease; Genitourinary system; Health; Herpesviridae; Herpesviridae Infections; Human; Human Herpesvirus 4; Human Herpesvirus 8; Immune; Immune response; Infection; Inflammation; Inflammatory; Injury; Knowledge; Lung; Microbe; Molecular; Mucosal Immunity; Mucositis; Nucleic Acids; Oral; Oral cavity; Pathway interactions; Patients; Periodontitis; Proteins; Reagent; Research; Role; Site; Skin; Virus; Virus Diseases; Work; clinical investigation; deamidation; feeding; gastrointestinal; microbiome; microbiota; pathogen; peri-implantitis; response

Abstract Inflammation is the body's response to damage induced by physical injury or pathogen infection. The oral cavity, gastrointestinal track, skin, lung and urogenital track represent distinct anatomical sites where host cells interface extensively with diverse microbes, presenting ample opportunities for infection and inflammation. Recent advances have uncovered pivotal roles of microbiota, primarily from the gut, in human health and disease. Our understanding in mucosal immunity of the other sites, particularly the oral cavity, is extremely limited. How viruses, in addition to the microbiome, contribute to oral inflammation and diseases thereof remains unknown. Emerging clinical studies revealed that human herpesviruses (e.g., Epstein-Barr virus and cytomegalovirus) were frequently detected in the oral cavity of patients with severe forms of inflammatory diseases, such as periodontitis, peri-implantitis and mucositis. Other studies also suggest that inflammation can promote herpesvirus reactivation and replication in the oral cavity. However, how herpesviruses contribute to oral inflammation and the underlying molecular mechanisms have never been explored. Built on our recent discovery that herpesviruses deploy protein deamidation to manipulate host immune response, this study will directly address the above knowledge gap with research answering the following questions: 1) What is the role of herpesvirus infection in oral inflammatory diseases; 2) How do nucleic acid sensing pathways operate in oral immune defense and impact oral inflammatory disease; 3) How does herpesviral evasion of nucleic acid- sensing pathways impinge on oral inflammation; 4) What are the regulatory role of protein deamidation in viral infection and immune defense in the oral cavity; and 5) Can we leverage protein deamidation to tame oral inflammation and treat oral inflammatory diseases. This work will illuminate the role and molecular basis of innate immune sensing, herpesvirus infection and protein deamidation in oral inflammation. Harnessing our knowledge of protein deamidation, we will develop key reagents to rectify chronic inflammation and treat oral inflammatory diseases.

抽象的 炎症是人体对身体损伤或病原体感染引起的损害的反应。口头 空腔，胃肠道轨迹，皮肤，肺和泌尿生殖器轨迹代表不同的解剖部位，其中宿主细胞 界面广泛地与不同的微生物，为感染和炎症提供了充足的机会。 最近的进步发现了微生物群的关键作用，主要来自肠道，在人类健康和 疾病。我们对其他部位的粘膜免疫的理解，尤其是口腔，非常 有限的。除了微生物组外，病毒如何导致口腔炎症及其疾病 仍然未知。 新兴的临床研究表明，人疱疹病毒（例如，爱泼斯坦 - 巴尔病毒和巨细胞病毒） 经常在患有严重形式炎症性疾病的患者的口腔中检测到 牙周炎，种植体炎和粘膜炎。其他研究还表明，炎症可以促进 口腔中的疱疹病毒重新激活和复制。但是，疱疹病毒如何贡献口腔 炎症和潜在的分子机制从未探索过。建立在我们最近的 发现疱疹病毒部署蛋白质脱氨基以操纵宿主免疫反应，这项研究将 通过研究回答以下问题直接解决上述知识差距：1） 口腔炎症性疾病中的疱疹病毒感染； 2）核酸传感途径如何在口腔中运行 免疫防御和撞击口腔炎症疾病； 3）如何逃避核酸 - 感知途径会影响口腔炎症； 4）蛋白质脱氨酸在病毒中的调节作用是什么 口腔中的感染和免疫防御； 5）我们可以利用蛋白质脱氨酸来驯服口服 炎症和治疗口腔炎症性疾病。这项工作将阐明 口腔炎症中的先天免疫感应，疱疹病毒感染和蛋白质脱氨酸。利用我们的 了解蛋白质脱氨酸，我们将开发关键试剂以纠正慢性炎症和治疗口腔 炎症性疾病。