The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species

Bettina Gruhne; Ramakrishna Sompallae; Diego Marescotti; Siamak Akbari Kamranvar; Stefano Gastaldello; Maria G. Masucci

doi:10.1073/pnas.0810619106

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The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species

Journal article

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The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species

Bettina Gruhne, Ramakrishna Sompallae, Diego Marescotti, Siamak Akbari Kamranvar, Stefano Gastaldello and Maria G. Masucci

Proceedings of the National Academy of Sciences - PNAS, Vol.106(7), pp.2313-2318

From the Cover

02/17/2009

DOI: 10.1073/pnas.0810619106

PMCID: PMC2650153

PMID: 19139406

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Abstract

The Epstein–Barr virus (EBV) nuclear antigen (EBNA)-1 is the only viral protein expressed in all EBV-carrying malignancies, but its contribution to oncogenesis has remained enigmatic. We show that EBNA-1 induces chromosomal aberrations, DNA double-strand breaks, and engagement of the DNA damage response (DDR). These signs of genomic instability are associated with the production of reactive oxygen species (ROS) and are reversed by antioxidants. The catalytic subunit of the leukocyte NADPH oxidase, NOX2/gp91 phox , is transcriptionally activated in EBNA-1–expressing cells, whereas inactivation of the enzyme by chemical inhibitors or RNAi halts ROS production and DDR. These findings highlight a novel function of EBNA-1 and a possible mechanism by which expression of this viral protein could contribute to malignant transformation and tumor progression.

Biological Sciences

Details

Title: Subtitle: The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species
Creators: Bettina Gruhne - Karolinska Institutet
Ramakrishna Sompallae - Karolinska Institutet
Diego Marescotti - Karolinska Institutet
Siamak Akbari Kamranvar - Karolinska Institutet
Stefano Gastaldello - Karolinska Institutet
Maria G. Masucci - Karolinska Institutet
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.106(7), pp.2313-2318
Series: From the Cover
DOI: 10.1073/pnas.0810619106
PMID: 19139406
PMCID: PMC2650153
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 02/17/2009
Academic Unit: Pathology
Record Identifier: 9984622759302771

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