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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
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Cell and Molecular Biology Karolinska Institutet, Stockholm, Sweden. (Frisan)ORCID iD: 0000-0002-1209-0942
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 1, p. 98-109Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. Vol. 144, no 1, p. 98-109
Keywords [en]
DNA damage, Epstein-Barr virus, Gram-negative bacteria, cytolethal distending toxin, virus reactivation
National Category
Cell and Molecular Biology Microbiology in the medical area
Research subject
Microbiology; Infectious Diseases
Identifiers
URN: urn:nbn:se:umu:diva-154014DOI: 10.1002/ijc.31652ISI: 000451479900010PubMedID: 29978480OAI: oai:DiVA.org:umu-154014DiVA, id: diva2:1269844
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2018-12-12Bibliographically approved

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Frisan, Teresa

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