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: 9461929
• 负责人: Pinghui Feng
• 金额: $ 67.72万
• 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/9461929
• 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 炎症是身体对身体伤害或病原体感染引起的损害的反应。口头的 腔、胃肠道、皮肤、肺和泌尿生殖道代表宿主细胞所处的不同解剖部位 与多种微生物广泛接触，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群（主要来自肠道）在人类健康和 疾病。我们对其他部位（特别是口腔）的粘膜免疫的了解非常深刻 有限的。除了微生物组之外，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，人类疱疹病毒（例如 Epstein-Barr 病毒和巨细胞病毒） 经常在患有严重炎症性疾病的患者的口腔中检测到，例如 牙周炎、种植体周围炎和粘膜炎。其他研究也表明炎症可以促进 疱疹病毒在口腔中重新激活和复制。然而，疱疹病毒如何促进口腔 炎症及其潜在的分子机制从未被探索过。建立在我们最近的 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 通过研究回答以下问题来直接解决上述知识差距：1）作用是什么 口腔炎症性疾病中疱疹病毒感染的影响； 2) 核酸传感途径如何在口腔中发挥作用 免疫防御和影响口腔炎症； 3) 疱疹病毒如何逃避核酸- 传感通路影响口腔炎症； 4）蛋白质脱酰胺作用在病毒中的调节作用是什么 口腔感染与免疫防御； 5) 我们能否利用蛋白质脱酰胺作用来驯服口腔 炎症并治疗口腔炎症疾病。这项工作将阐明其作用和分子基础 先天免疫感应、疱疹病毒感染和口腔炎症中的蛋白质脱酰胺。利用我们的 掌握蛋白质脱酰胺的知识，我们将开发纠正慢性炎症和治疗口腔疾病的关键试剂 炎症性疾病。