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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
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- Frisan, Teresa, 1967- (author)
- Karolinska Institutet,Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Department of Cell and Molecular Biology Karolinska Institutet, Stockholm, Sweden,Frisan
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- Nagy, Noemi (author)
- Karolinska Institutet
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- Chioureas, Dimitrios (author)
- Karolinska Institutet
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- Terol, Marie (author)
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- (creator_code:org_t)
- 2018-10-29
- 2019
- English.
- In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:1, s. 98-109
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- DNA damage
- Epstein-Barr virus
- Gram-negative bacteria
- cytolethal distending toxin
- virus reactivation
- mikrobiologi
- Microbiology
- Infectious Diseases
- infektionssjukdomar
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- ref (subject category)
- art (subject category)
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