UKY DENTAL COBRE: ORAL INFECTIONS: VIRAL INFECTIONS IN CHRONIC ORAL DISEASES

英国牙科 COBRE：口腔感染：慢性口腔疾病中的病毒感染

• 批准号: 7960559
• 负责人: Mengtao Li
• 金额: $ 18.77万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960559
• 关键词: Actinobacillus actinomycetemcomitans; Address; Animals; Bacteria; Centers of Research Excellence; Chronic; Clinical; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Dental; Dental Plaque; Epstein-Barr Virus Infections; Fibroblasts; Funding; Fusobacterium nucleatum; Genes; Gingiva; Goals; Grant; Herpesviridae; Human; Immune response; Infection; Institution; Lytic; Modeling; Molecular; Mouth Diseases; Oral; Pathogenesis; Patients; Periodontal Diseases; Periodontitis; Phagocytosis; Porphyromonas gingivalis; Process; Protein Isoforms; Rat Cytomegalovirus; Rattus; Research; Research Personnel; Resources; Role; Saliva; Sampling; Site; Source; Streptococcus gordonii; Systemic disease; Testing; Time; Tissues; United States National Institutes of Health; Virus; Virus Diseases; base; human DNA; immunoregulation; macrophage; microorganism; novel; oral cavity epithelium; oral infection; pathogen; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although bacteria are the primary pathogens in periodontitis, human herpesviruses have a purported relationship with inflamed periodontal tissues. This could be important because herpesviruses modulate host immune responses through a variety of mechanisms. The goal of this research was to test the hypothesis that herpesviruses enhance the pathogenesis of periodontal diseases. Our hypothesis is being examined using three approaches: 1) determine the role of herpesviruses in periodontitis by analyzing clinical samples from patients with and without periodontal disease, 2) investigating the ability of herpesvirus to enhance the progression of periodontitis in the rat model; and 3) define mechanisms of immunomodulation by cytomegalovirus (CMV). To address component 1, we are analyzing dental plaque from healthy and diseased sites and parallel saliva samples from 100 patients with periodontal disease. Real-time PCR is being used to detect DNA of human herpesvirus in the samples obtained longitudinally over 6 months. In the second project, the rat CMV (RCMV) Maastricht strain has been obtained, propagated and titered. Animals have been inoculated with P. gingivalis and/or RCMV to establish infections and evaluate the periodontal response. In the study of molecular mechanisms of immunomodulation by CMV, we have cloned and characterized novel isoforms of CMV vIL-10 gene and recently cloned EBV vIL-10. Because these viruses can modulate the immune response, we have initiated studies that determine their role in modulating the host response of oral epithelia and gingival fibroblasts against invasion by periodontal bacterial pathogens. Using human primary macrophages and THP-1 derived macrophage as models, we have studied the effects of CMV and EBV infection on the function of macrophage in response to four oral microorganisms: P. gingivalis (Pg) and A. actinomycetemcomitans (Aa); opportunistic pathogen, F. nucleatum (Fn); and non-pathogen S. gordonii (Sg), and have demonstrated that CMV and EBV alters the TNFa response of macrophages to these oral microorganisms. We are in the process of determining if lytic genes of CMV and/or EBV are required for the altered response and whether these viruses also inhibit the phagocytosis activity of macrophages to these bacteria.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尽管细菌是牙周炎中的主要病原体，但人疱疹病毒与发炎的牙周组织有着关系。这可能很重要，因为疱疹病毒通过多种机制调节宿主免疫反应。 这项研究的目的是检验疱疹病毒增强牙周疾病发病机理的假设。 我们的假设正在使用三种方法进行检查：1）通过分析和没有牙周疾病患者的临床样本来确定疱疹病毒在牙周炎中的作用，2）研究疱疹病毒在大鼠模型中增强牙周炎进展的能力； 3）定义巨细胞病毒（CMV）的免疫调节机制。 为了解决组件1，我们正在分析来自健康和患病部位的牙齿牙菌斑，以及100例牙周疾病患者的平行唾液样品。 实时PCR用于检测在6个月内纵向获得的样品中人类疱疹病毒的DNA。 在第二个项目中，已经获得，繁殖和替代大鼠CMV（RCMV）Maastricht菌株。 已接种牙龈疟原虫和/或RCMV，以建立感染并评估牙周反应。在CMV免疫调节的分子机制中，我们克隆并表征了CMV VIL-10基因的新型同工型，并最近克隆了EBV VIL-10。由于这些病毒可以调节免疫反应，因此我们开始了研究，这些研究确定了它们在调节口腔上皮和牙龈成纤维细胞对牙周细菌病原体侵袭的宿主反应中的作用。 我们使用人类的原发性巨噬细胞和THP-1衍生的巨噬细胞作为模型，我们研究了CMV和EBV感染对四种口腔微生物的巨噬细胞功能的影响：牙龈疟原虫（PG）和A. actinomysymomycetemcetemcomitans（AA）；机会性病原体F. nucleatum（FN）；和非致病原链球菌（SG），并证明CMV和EBV改变了巨噬细胞对这些口服微生物的TNFA反应。我们正在确定反应改变的CMV和/或EBV是否需要裂解基因，以及这些病毒是否还抑制了巨噬细胞对这些细菌的吞噬作用。