Human Herpesvirus Impact on Periodontal Inflammation

人类疱疹病毒对牙周炎症的影响

• 批准号: 10214593
• 负责人: Afsar Raza Naqvi
• 金额: $ 37.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214593
• 关键词: Actinobacillus actinomycetemcomitans; Address; Adult; Affect; Antigen Presentation Pathway; Antigen-Presenting Cells; Antigens; Bacteriophages; Biological Process; Biopsy; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Culture Techniques; Cell physiology; Cells; Clinical; Cytomegalovirus; Cytotoxic T-Lymphocytes; DNA Viruses; Data; Dendritic Cells; Dentistry; Detection; Diagnosis; Diagnostic; Disease; Doctor of Philosophy; Epithelial Cells; Exposure to; Functional disorder; Generations; Genes; Gingiva; Goals; HHV-6B; Helper-Inducer T-Lymphocyte; Herpesviridae; Herpesviridae Infections; Herpesvirus 1; High Prevalence; Human; Human Herpesvirus 2; Human Herpesvirus 4; Human Herpesvirus 8; Human body; Immune; Immune Evasion; Immune response; Immune system; In Situ Hybridization; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Innate Immune Response; Knowledge; Life Cycle Stages; Lytic; Lytic Phase; Malignant Neoplasms; Measures; Mediating; Medicine; Messenger RNA; MicroRNAs; Microbe; Myeloid Cells; Oral; Oral cavity; Oral mucous membrane structure; Pathogenesis; Pathway interactions; Patients; Periodontitis; Periodontium; Phagocytosis; Porphyromonas gingivalis; Prevention strategy; Process; RNA; Role; Sampling; Site; Small RNA; T cell response; T-Lymphocyte; Testing; Tissues; Tooth Tissue; Transcript; Viral; Viral Genome; Virion; Virus; Virus Diseases; Virus Latency; adaptive immune response; bone; cytokine; cytotoxic; dental biofilm; differential expression; functional plasticity; human disease; immunoregulation; insight; keratinocyte; macrophage; member; microbial; novel; novel therapeutics; oral bacteria; oral tissue; overexpression; pathogen; periopathogen; polarized cell; prognostic; response; synergism; therapeutic target; uptake; viral DNA; virus host interaction

Human Herpesvirus Impact on Periodontal Inflammation Afsar Raza Naqvi, Ph.D. Human Herpesviruses (HHV) are large, enveloped DNA viruses that establish lifelong latency. In adult humans, one or more types of viruses are persistently detected signifying HHV adaptation inside human body. Multiple lines of evidence show higher prevalence of these viruses in various oral inflammatory diseases but how HHV exacerbate these infections remains unexplored. A unique feature of HHV, unlike other viruses, is that they also encode viral miRNAs (v-miRs). These viral microRNAs (vmiRs) are multifunctional as they regulate expression of both virus and host derived transcripts and thus control host-virus interaction. In this proposal, we will study the impact of five most common oral inflammatory diseases associated HHV viz., HCMV, HSV-1, EBV, KSHV and HHV-6B on periodontal inflammation, a highly common oral inflammatory disease. The levels of viral miRNAs will be quantified in patients with diseased gingiva and correlate with viral genome and life cycle associated transcripts. We aim to characterize the role of candidate vmiRs in regulating HHV infection in host gingival epithelial cells and macrophages. Identifying positive and negative regulatory v- miRs can yield novel insights into host-virus interaction. The impact of vmiRs on key biological functions of primary human oral keratinocytes and macrophages will be examined primarily by evaluating their influence on innate response against periopathogens (P. gingivalis and A. actinomycetemcomitans). This will shed novel insights into virus-bacterial synergy. Our next aim will test whether vmiRs can render host immune system dysfunctional. This will be examined by enforced expression of vmiRs in macrophages and dendritic cells. The key biological functions of these cells include pathogen uptake, antigen processing and presentation to T helper (CD4+) and T cytotoxic (CD8+) cells. In addition, we will assess the impact of v-miRs on the polarization of CD4+ T cells. The data generated will provide significant information to existing knowledge gaps. Interestingly, as vmiRs are not endogenous RNAs, they have the potential to be deployed as potential therapeutic targets. Given their immunomodulatory role, manipulation of these small RNAs may also be useful in the diagnosis and treatment of oral inflammatory diseases.

人类疱疹病毒对牙周炎的影响 Afsar Raza Naqvi博士 人类疱疹病毒(HHV)是一种大的包膜DNA病毒，可建立终身潜伏期。 在成人中，持续检测到一种或多种类型的病毒，这意味着HHV 人体内的适应。多条证据表明这种疾病的患病率更高。 各种口腔炎症性疾病中的病毒，但HHV如何加剧这些感染仍然存在 未被开发的。与其他病毒不同，HHV的一个独特特征是它们还编码病毒 MiRNAs(v-miRs)。这些病毒microRNAs(VmiR)是多功能的，因为它们调节 病毒和宿主来源的转录本的表达，从而控制宿主与病毒的相互作用。在……里面 在这个提案中，我们将研究五种最常见的口腔炎症性疾病的影响 HHV、HCMV、HSV-1、EBV、KSHV和HHV-6B对牙周炎的影响 非常常见的口腔炎症性疾病。病毒miRNAs的水平将在 牙周病患者与病毒基因组和生命周期的相关性 成绩单。我们的目标是表征候选vmiRs在调节HHV感染中的作用。 宿主牙龈上皮细胞和巨噬细胞。识别积极和消极的监管v- MIRS可以对宿主与病毒的相互作用产生新的见解。VmiRs对关键生物的影响 原代人类口腔角质形成细胞和巨噬细胞的功能将主要通过 评价它们对牙周病病原体(牙龈假单胞菌和牙周炎沙门氏菌)先天反应的影响。 伴生放线菌)。这将为病毒-细菌的协同作用带来新的见解。我们的下一个目标 将测试vmiRs是否会导致宿主免疫系统功能失调。这将由 巨噬细胞和树突状细胞中vmiRs的增强表达。关键的生物学功能 这些细胞包括病原体摄取、抗原处理和呈递给辅助性T细胞(CD4+) 和T细胞毒(CD8+)细胞。此外，我们还将评估v-mir对极化的影响。 CD4+T细胞的数量。生成的数据将为现有知识提供重要信息 差距。有趣的是，由于vmiR不是内源rna，它们具有部署的潜力。 作为潜在的治疗靶点。鉴于它们的免疫调节作用，操纵这些小的 RNA也可能在口腔炎症性疾病的诊断和治疗中有用。