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.
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