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.

摘要 炎症是身体对身体损伤或病原体感染造成的损害的反应。口服液 腔、胃肠道、皮肤、肺和泌尿生殖道代表宿主细胞的不同解剖位置 与各种微生物广泛接触，为感染和炎症提供了充足的机会。 最近的进展揭示了微生物区系的关键作用，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，特别是口腔粘膜免疫的了解是极其深刻的。 有限的。除微生物群外，病毒如何促进口腔炎症和口腔疾病 仍然不为人知。 新出现的临床研究表明，人类疱疹病毒(如Epstein-Barr病毒和巨细胞病毒) 在患有严重炎症性疾病的患者的口腔中经常检测到 牙周炎、种植周炎和粘膜炎。其他研究也表明，炎症可以促进 口腔内疱疹病毒的重新激活和复制。然而，疱疹病毒如何对口腔做出贡献 炎症及其潜在的分子机制从未被探索过。基于我们最新的 发现疱疹病毒利用蛋白质脱酰胺来操纵宿主免疫反应，这项研究将 直接解决上述知识差距与研究回答以下问题：1)角色是什么 口腔炎症性疾病中疱疹病毒感染的研究；2)核酸传感通路在口腔中是如何工作的 免疫防御和影响口腔炎症性疾病；3)疱疹病毒如何逃避核酸- 感觉通路影响口腔炎症；4)蛋白质脱酰胺在病毒中的调节作用是什么 口腔内的感染和免疫防御；以及5)我们能否利用蛋白质去酰胺化来驯服口腔 炎症和治疗口腔炎症性疾病。这项工作将阐明它的作用和分子基础。 口腔炎症中的先天免疫感知、疱疹病毒感染和蛋白质脱酰胺。利用我们的 了解蛋白质去酰胺化，我们将开发关键试剂来纠正慢性炎症和治疗口腔 炎症性疾病。