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.
Int J Cancer
; 144(1): 98-109, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-29978480
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Viral
/
Transformação Celular Neoplásica
/
Aggregatibacter actinomycetemcomitans
/
Herpesvirus Humano 4
/
Células Epiteliais
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suécia