Differential Bacterial induction of Oral Viral Pathogenesis

Herpesviral sequences are frequently copresent with bacterial infection at multiple sites including the gut and genital urinary tract. Recently, these polymicrobial infections have been detected in the oral cavity, particularly in severe cases of periodontits. Objective: The detection of replicating virus in these tissues has incited investigation of the relationship of bacterial infection to herpesviral reactivation. Discerning mechanisms of bacterial induced viral reactivation underpins the molecular basis of periodontal disease pathogenesis. We hypothesized that bacterial endproducts including short chain fatty acids (SCFA), lipopolysaccharide (LPS) and lipoteichoic (LTA) secreted by oral bacteria initiate viral reactivation from latency. Methods: Latently infected herpesvirus cell lines were incubated in vitro with crude spent media containing SCFA and baterial components of periodontal pathogens. Cells were assayed for promoter activation or state of infection. To determine mechanism of reactivation HDAC inhibition potential and PKC activity were measured. Fractionation was performed to determine the bacterial determinants key to viral reactivation. Results: Following incubation with crude spent media, viral immediate early promoters were activated, the viral early genes were upregulated and linear genomes were detected by Gardella analysis. Conclusions: HDAC inhibition activity as well as kinase activity increased significantly following oral pathogen spent media treatment. Interestingly, distinct oral bacterial pathogens differentially reactivated EBV, KSHV and HSV-1.