 "cancer")
Researchers have described in a study how the Epstein-Barr virus (EBV), the ubiquitous virus easily spread through bodily fluids, not only exploits genomic weaknesses to cause cancer, but also reduces the body's ability to suppress it.
The researchers at the University of California (UC) San Diego, US, said that more than 90 per cent of the world's population has been infected by the EBV, usually during childhood, and that while most of the infections it causes are mild and pass, the virus persists in the body, becoming latent or inactive, sometimes reactivating.
The EBV spreads easily through bodily fluids, primarily saliva, through activities such kissing, sharing drinks or using the same eating utensils.
The researchers' findings showed "how a virus can induce cleavage of human chromosome 11, initiating a cascade of genomic instability that can potentially activate a leukemia-causing oncogene and inactivate a major tumour suppressor," said senior study author Don Cleveland, professor at UC San Diego School of Medicine.
They have published their findings in the journal Nature.
Chromosome 11, one of the 23 pairs of chromosomes in humans, spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 per cent of the total DNA in cells.
Throughout every person's genome or full set of genes are fragile sites, which are specific chromosomal regions more likely to produce mutations, breaks or gaps when replicating. While some are rare and some are common, all are associated with disorders and disease, sometimes heritable conditions, sometimes not, such as many cancers.
"[The study is] the first demonstration of how cleavage of a 'fragile DNA' site can be selectively induced," said Cleveland.
In this study, Cleveland and colleagues focussed on EBNA1, a viral protein that persists in cells infected with EBV.
Previously known to bind at a specific genomic sequence in the EBV genome at replication, the researchers found that EBNA1 also binds a cluster of EBV-like sequences at a fragile site on human chromosome 11.
An increasing abundance of the protein at this fragile site was found to trigger chromosomal breakage.
Prior research has shown that EBNA1 inhibits p53, a gene that plays a key role in controlling cell division and cell death. It also suppresses tumour formation when normal. Mutations of p53, on the other hand, are linked to cancer cell growth.
Upon examining the whole-genome sequencing data for 2,439 cancers across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes project, the researchers found that cancer tumours with detectable EBV revealed higher levels of chromosome 11 abnormalities, including in 100 per cent of the head and neck cancer cases.
"For a ubiquitous virus that is harmless for the majority of the human population, identifying at-risk individuals susceptible to the development of latent infection-associated diseases is still an ongoing effort," said the study's first author Julia Li, a postdoctoral fellow in Cleveland's lab.
"Going forward, this knowledge paves the way for screening risk factors for the development of EBV-associated diseases. Moreover, blocking EBNA1 from binding at this cluster of sequences on chromosome 11 can be exploited to prevent the development of EBV-associated diseases," said Li.
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