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.

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