Cancer danger: Herpes virus causes the cells to degenerate

According to this, viral proteins dock to a particularly fragile spot on our chromosome 11 and cause breaks there. This in turn promotes the development of cancer, as the team in „Nature“ reported. The new findings now open up the opportunity to prevent this degeneration in a targeted manner and also to identify people who are particularly at risk.

Around 90 percent of us carry the Epstein-Barr virus (EBV) – mostly unnoticed and since early childhood. In some cases, however, the pathogen belonging to the herpes viruses can make you ill: it causes glandular fever and is suspected of Multiple Sclerosis, Long Covid and to promote chronic fatigue syndrome. EBV is also considered a possible cause of several cancers, including Hodgkin’s lymphoma and pharynx cancer.

In addition to the Epstein-Barr virus (EBV) also include

• the Varizella-Zoster-Virus (which causes chickenpox and shingles)
• the Cytomegalievirus
• the Humane Herpesvirus 6A, 6B and 7 as well as
• the Kaposi’s sarcoma-associated herpesvirus

to the herpes virus.

Targeting viral protein

But how can the Epstein-Barr virus cause a cancerous tumor? Julia Su Zhou Li from the University of California in San Diego and her colleagues may have discovered the mechanism behind it. They investigated a well-known characteristic of the virus: EBV leaves behind the viral protein EBNA1 in infected cells. This binds in a kind of feedback to a specific DNA sequence in the genome of the virus, but can also attach itself to human DNA.

This is where the study by Li and her team comes in: With the help of various human cell cultures, they investigated where exactly the virus protein docks in the genome. They discovered a striking accumulation of attached EBNA1 proteins in a section of chromosome 11. More detailed analyzes revealed that the genome there contains numerous copies of a DNA sequence that resembles the docking sequence in the Epstein-Barr gene code. This allows the viral EBNA1 protein to dock onto our DNA.

Fragile site in the chromosome

The interesting thing about it is that the viral protein binds to a so-called fragile point on the chromosome. There, the DNA is particularly susceptible to damage, mutations and breaks during cell division. “Such spots tend to fracture when exposed to additional stressors,” Li and her colleagues explain. Appropriately, their analyzes revealed that the docking of the viral EBNA1 protein breaks the DNA strand at this point.

“We therefore suspected that the accumulation of EBNA1 at this already unstable site could cause a break in the chromosome at position 11q23,” the researchers write. This was confirmed in the cell division of the affected cells: “Around 40 percent of the mitotic cells contained one or more chromosomes that appeared to be broken at the EBNA1 docking site.” This break in the eleventh chromosome was also retained in subsequent cell divisions.

“We have thus discovered a previously unrecognized connection between EBV and changes in the eleventh chromosome,” Li and her colleagues state. The experiment shows for the first time how a viral protein breaks a fragile point in the genome.

Chromosomal damage can also be detected in tumor data

Such damage to DNA is considered to be one of the factors that can trigger cell degeneration and thus cancer. To check whether this is also the case with the chromosome break caused by the Epstein-Barr virus protein, the researchers next looked for signs of this break in DNA sequences of cancer tumors.

The analysis of the genome data of 2,439 tumor types and 38 types of cancer revealed: The cancer tumors of patients with a latent EBV infection had abnormalities on chromosome 11 significantly more frequently of EBV-positive ear and throat tumors contained changes on chromosome 11,” Li and her team report.

Opportunity for early detection and prevention

According to the researchers, this could explain why latent infection with the Epstein-Barr virus, and especially the resurgence of this virus, increases the risk of certain types of cancer. “We assume that the reactivation of the virus in the affected cells leads to a break in the eleventh chromosome by the viral EBNA1 protein,” the team explains. The risk of such genetic damage is all the higher, the more copies of the viral docking sequence a person carries at this genome position. This explains why not everyone infected with EBV develops cancer.

“This finding opens up the possibility of specifically screening people for this risk factor for EBV-related diseases,” says senior author Don Cleveland of the University of California. “Furthermore, this could be used to prevent the onset of such diseases by blocking EBNA1 attachment to these genomic sequences.”

Quelle: University of California – San Diego

This article was written by Nadja Podbregar