Three Epstein–Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints
Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human malignancies, but its contribution to tumorigenesis is not well understood. EBV carriage is associated with increased genomic instability in Burkitt's lymphoma, suggesting that viral products may induce this tumor phenotype. Using a panel of transfected sublines of the B-lymphoma line BJAB expressing the viral genes associated with latent infection, we show that the EBV nuclear antigens, EBNA-1 and EBNA-3C, and the latent membrane protein 1, LMP-1, independently promote genomic instability, as detected by nonclonal chromosomal aberrations, DNA breaks and phosphorylation of histone H2AX. EBNA-1 promotes the generation of DNA damage by inducing reactive oxygen species (ROS), whereas DNA repair is inhibited in LMP-1-expressing cells through downregulation of the DNA damage-sensing kinase, ataxia telangiectasia mutated (ATM), reduction of phosphorylation of its downstream targets Chk2 and inactivation of the G(2) checkpoint. EBNA-3C enhances the propagation of damaged DNA through inactivation of the mitotic spindle checkpoint and transcriptional downregulation of BubR1. Thus, multiple cellular functions involved in the maintenance of genome integrity seem to be independently targeted by EBV, pointing to the induction of genomic instability as a critical event in viral oncogenesis.
Pharmacology, Toxicology and Pharmaceutical Science
3
4%
Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 December 2025.
All research outputs
#10,120,774
of 31,301,153 outputs
Outputs from Oncogene
#5,764
of 13,249 outputs
Outputs of similar age
#45,554
of 126,958 outputs
Outputs of similar age from Oncogene
#34
of 63 outputs
Altmetric has tracked 31,301,153 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 13,249 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 126,958 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
