The Epstein-Barr virus causes infectious mononucleosis and similar ailments, though often there are no symptoms. Most infections are mild and pass, but the virus persists in the body, becoming latent or inactive, sometimes reactivating. Long-term latent infections are associated with several chronic inflammatory conditions and multiple cancers.
In a recent paper it was described for the first time how the virus exploits genomic weaknesses to cause cancer while reducing the body’s ability to suppress it.
“The 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 senior study author Don Cleveland.
“It’s the first demonstration of how cleavage of a ‘fragile DNA’ site can be selectively induced.”
Cleveland and colleagues focus on EBNA1, a viral protein that persists in cells infected with EBV. EBNA1 was previously known to bind at a specific genomic sequence in the EBV genome at the origin of replication. The researchers found that EBNA1 also binds a cluster of EBV-like sequences at a fragile site on human chromosome 11 where increasing abundance of the protein triggers chromosomal breakage.
Scientists found that cancer tumors with detectable EBV revealed higher levels of chromosome 11 abnormalities, including 100% 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.
Julia Su Zhou Li, Ammal Abbasi, Dong Hyun Kim, Scott M. Lippman, Ludmil B. Alexandrov, Don W. Cleveland. Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats. Nature, 2023; 616 (7957): 504 DOI: 10.1038/s41586-023-05923-x
University of California – San Diego. “How a virus causes chromosomal breakage, leading to cancer: The ubiquitous Epstein-Barr virus targets ‘fragile DNA,’ triggering dysfunction that is associated with a variety of cancers.” ScienceDaily. ScienceDaily, 13 April 2023. <www.sciencedaily.com/releases/2023/04/230413231640.htm>.
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