Bacteria-mediated reactivation of gammaherpesviruses

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  • Morris, Terry
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Gu, Fang
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Rothwell, RoShaunna
    • Affiliation: School of Dentistry, Department of Dental Ecology
  • Webster-Cyriaque, Jennifer
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
Abstract
  • Significant morbidity is associated with the synergistic and inhibitory interactions of bacteria, viruses, parasites, and fungi. The oral cavity, gut, and genitourinary tract are home to many of these organisms and are the site of virus-associated malignancies that affect millions worldwide. Yet little is known with regard to the cellular and molecular interactions of viral pathogens with the normal flora as well as the interactions among pathogens themselves. Our laboratory is interested in understanding the role of factors present within the immediate environment that may influence reactivation of persistent infection and pathogenesis. Our central hypothesis is that viral-bacterial interactions foster enhanced pathogen replication and modulation of the immune response in the mouth, GI tract, and genito-urinary tract. The detection of replicating virus in these tissues has incited investigation into the relationship between bacterial infection and herpesviral reactivation. We hypothesized that bacterial end-products including short chain fatty acids (SCFA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) secreted by oral bacteria initiate viral reactivation from latency. Latently infected EBV, KSHV, and MHV 68 cell lines were incubated with crude spent media containing secreted SCFA, and components of bacterial pathogens (E. faecalis, Bacteriodes, Prevotella, Porphomonas, and Fusiobacterium Nucleatum). Cells were then assayed for viral promoter activation, promoter-protein interactions, and state of infection. Following incubation with crude spent media, viral immediate early promoters were activated, the viral early genes were upregulated as determined by RT PCR and western blot, and linear genomes were detected. HDAC inhibition activity as well as protein kinase C activity increased significantly following treatment with bacterial spent media. KSHV and EBV were consistently reactivated by bacterial metabolites but the mechanism of reactivation was both bacteria, virus, and cell type specific. Interestingly, EBV was preferentially reactivated following toll like receptor stimulation while KSHV and HSV-1 reactivation occurred following HDAC inhibition. In conclusion, these studies provide significant insights to gammaherpesreactivation that may occur in vivo via pathogen-pathogen interaction.
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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Terry Morris et al.; licensee BioMed Central Ltd.
Journal title
  • Infectious Agents and Cancer
Journal volume
  • 5
Journal issue
  • Suppl 1
Page start
  • A6
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1750-9378
Bibliographic citation
  • Infectious Agents and Cancer. 2010 Oct 11;5(Suppl 1):A6
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • August 23, 2012

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