The Role of Periodontal Bacteria and Epigenetic Modifications on Human Papillomavirus Pathogenicity

• Main Author: Cunningham Glasspoole, Danielle Louise
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01.01.2019
• Subjects: Dentistry; Microbiology; Virology
• ISBN: 1392514282; 9781392514283

The oral cavity is home to nearly 700 species of bacteria and is the site of chronic inflammation (periodontitis) caused by the accumulation of virulent bacteria (bacterial dysbiosis). In addition to periodontal disease the oral cavity is subject to viral infection by Human Papillomavirus (HPV), the most common viral sexually transmitted infection (STI). HPV infection has a causal link to over 99% of cervical cancer cases and an increasing number of oral cancer cases. There is increasing evidence that bacterial coinfections can alter viral pathogenicity including reactivation of latent virally infected cells. Despite the commonality of bacterial and viral infections in the mouth, few have studied the link between bacterial species associated with chronic periodontal disease and HPV pathogenesis. The studies described in this manuscript are aimed to define the link between periodontal disease and HPV pathogenesis using population data. The study also examines HPV oncogene expression in the presence of periodontal bacterial metabolites. The population based study reveals approximately 3.5-fold increased risk of having oral HPV with moderate and sever periodontal disease respectively. The in-vitro studies revealed HPV oncogene expression (E6/E7) increases when virally infected cells are exposed to metabolites from periodontal pathogens, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn). Further Pg and Fn increase histone modifications surrounding the viral promoter that are associated with increases in viral transcripts and an overall open chromatin conformation. Additionally, these studies describe the genomic features surrounding the integration sites of several DNA tumor viruses including HPV. This study found open chromatin regions and activating histone modifications as some of the prediction features for sites of HPV integration in HPV infected epithelial cells.