A bacterial genotoxin causes virus reactivation and genomic instability in Epstein-Barr virus infected epithelial cells pointing to a role of co-infection in viral oncogenesis.
We have addressed the role of bacterial co-infection in viral oncogenesis using as model Epstein-Barr virus (EBV), a human herpesvirus that causes lymphoid malignancies and epithelial cancers. Infection of EBV carrying epithelial cells with the common oral pathogenic Gram-negative bacterium Aggregatibacter actinomycetemcomitans (Aa) triggered reactivation of the productive virus cycle. Using isogenic Aa strains that differ in the production of the cytolethal distending toxin (CDT) and purified catalytically active or inactive toxin, we found that the CDT acts via induction of DNA double strand breaks and activation of the Ataxia Telangectasia Mutated (ATM) kinase. Exposure of EBV-negative epithelial cells to the virus in the presence of sub-lethal doses of CDT was accompanied by the accumulation of latently infected cells exhibiting multiple signs of genomic instability. These findings illustrate a scenario where co-infection with certain bacterial species may favor the establishment of a microenvironment conducive to the EBV-induced malignant transformation of epithelial cells.
['Frisan|Teresa|T|0000-0002-1209-0942', 'Nagy|Noemi|N|', 'Chioureas|Dimitrios|D|', 'Terol|Marie|M|', 'Grasso|Francesca|F|', 'Masucci|Maria G|MG|0000-0002-5541-2809']
D016976:Aggregatibacter actinomycetemcomitans D001427:Bacterial Toxins D045744:Cell Line, Tumor D002471:Cell Transformation, Neoplastic D053903:DNA Breaks, Double-Stranded D004847:Epithelial Cells D004854:Herpesvirus 4, Human D054884:Host-Pathogen Interactions D006801:Humans D056265:Microbial Interactions D009153:Mutagens D014775:Virus Activation
virus reactivation Epstein-Barr virus cytolethal distending toxin DNA damage Gram-negative bacteria