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: 7382119
• 负责人: Mengtao Li
• 金额: $ 23.02万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382119
• 关键词: UKY; DENTAL; COBRE; ORAL; INFECTIONS

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). We have initiated a plan to recruit 100 patients with periodontal disease and collect dental plaques and saliva samples. Real-time PCR will be used to detect DNA of human herpesvirus in plaque from healthy and diseased sites and parallel saliva samples. This method that has been successfully used to identify all 8 HHVs in saliva is being optimized to detect viral DNA in plaque. In the second project, we have obtained rat CMV (RCMV) Maastricht strain, propagated lab stocks and obtained titers on the virus. Animal inoculation(s) with P. gingivalis and/or RCMV will be initiated in early summer 2005. In the study of molecular mechanisms of immunomodulation by CMV, we have successfully constructed and purified a recombinant CMV that expresses GFP (green fluorescence protein). In addition, we cloned CMV vIL-10 gene. We discovered 5 previously unidentified vIL-10 isoforms. We are in the process of characterizing 8 different vIL-10 isoforms in vitro and analyzing their amino acid sequences using bioinformatics methods. Because CMV vIL-10 is a potent immune suppressor, we are initiating study to determine its roles in modulating the host response of oral epithelia and gingival fibroblasts against bacterial invasion.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。虽然细菌是牙周炎的主要病原体，但人类疱疹病毒与炎症的牙周组织有据称的关系。这一点可能很重要，因为疱疹病毒通过各种机制调节宿主的免疫反应。这项研究的目的是验证疱疹病毒增强牙周病发病机制的假设。我们的假设正在用三种方法进行检验：1)通过分析患有和不患有牙周病的患者的临床样本，确定疱疹病毒在牙周炎中的作用；2)在大鼠模型中研究疱疹病毒促进牙周炎进展的能力；以及3)确定巨细胞病毒(CMV)的免疫调节机制。我们已经启动了一项计划，招募100名牙周病患者，并收集牙菌斑和唾液样本。实时定量聚合酶链式反应将用于检测健康和疾病部位斑块以及平行唾液样本中的人类疱疹病毒DNA。这种方法已经成功地用于识别唾液中的所有8种HHV，目前正在优化以检测菌斑中的病毒DNA。在第二个项目中，我们获得了大鼠巨细胞病毒(RCMV)马斯特里赫特株，繁殖了实验室的股票，并获得了病毒的效价。2005年初夏将开始动物接种(S)牙龈假单胞菌和/或巨细胞病毒。在研究CMV免疫调节的分子机制方面，我们成功构建并纯化了表达绿色荧光蛋白(GFP)的重组CMV。此外，我们还克隆了CMV VIL-10基因。我们发现了5种以前未知的VIL-10亚型。我们在体外鉴定了8种不同的VIL-10亚型，并用生物信息学方法分析了它们的氨基酸序列。由于CMV VIL-10是一种有效的免疫抑制因子，我们正在开展研究，以确定其在调节口腔上皮细胞和牙龈成纤维细胞对细菌入侵的宿主反应中的作用。