A group of researchers discovered that the Epstein-Barr virus (EBV) exploits human genomic weaknesses to cause cancer and suppress the body’s defenses.
The study shows that the EBNA1 protein binds to a fragile site on human chromosome 11, leading to chromosomal breakage and genomic instability that can result in cancer. This discovery may help identify risk factors and develop preventive strategies for EBV-associated diseases.
The Epstein-Barr virus (EBV) is easily spread through body fluids, mainly saliva. More than 90% of the world’s population has been infectedusually during childhood, reported the Sci Tech Daily.
EBV causes infectious mononucleosis and similar illnesses, although there are often no symptoms. Most infections are mild, but the virus persists in the body, becoming latent or inactive and sometimes reactivating. Long-term latent infections are associated with several chronic inflammatory conditions and multiple cancers.
In a new article, recently published in natureresearchers at the University of California at San Diego, in the United States, have described for the first time how the virus exploits genomic weaknesses to cause cancer, while reducing the body’s ability to suppress it.
These findings show “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 tumor suppressor,” said Don Cleveland, one of the study’s authors.
Throughout each person’s genome there are fragile points, specific chromosomal regions more likely to produce mutations, breaks or gaps when they reproduce. Some are rare, some common; all are associated with disorders and diseases, sometimes with hereditary conditions.
In the new study, Cleveland and colleagues focus on EBNA1, a protein that persists in EBV-infected cells. It was previously known that EBNA1 bound to a specific genomic sequence in the EBV genome.
The researchers have now discovered that EBNA1 also binds a cluster of EBV-like sequences to a weak point on human chromosome 11, where the increasing abundance of the protein triggers chromosome breakage.
Other previous research has shown that EBNA1 inhibits p53, a gene that plays a key role in controlling cell division and cell death. It also suppresses the formation of tumors when normal. Mutations of p53, on the other hand, are linked to the growth of cancer cells.
When the scientists examined whole-gene sequencing data for 2,439 cancers in 38 tumor types, they found that cancerous tumors with detectable EBV revealed higher levels of chromosome 11 abnormalities, including 100% of head and neck cancer cases.
“For a virus that is ubiquitous and harmless to the majority of the human population, identifying risk individuals susceptible to the development of diseases associated with latent infections it is still an ongoing effort”said Julia Li, another of the study’s authors.
“This finding suggests that susceptibility to EBNA1-induced fragmentation of chromosome 11 depends on controlling the levels of EBNA1 produced in latent infection, as well as the genetic variability of the number of EBV-like sequences present on chromosome 11 in each individual,” he explained.
“In the future, this knowledge pave the way for risk factor screening for the development of EBV-associated diseases. Furthermore, blocking EBNA1 binding in this group of sequences on chromosome 11 could be exploited to prevent the development of virus-associated diseases,” he concluded.
ZAP // 
