New Genetic Research Shows How Epstein-Barr Virus Leads to Cancer

Researchers in the United Kingdom have made a new genetic discovery in the link between Epstein-Barr virus and related cancers, including a potential way to stop the cancer-causing effects of these infections.

As one of the most common human viruses in the world, the Epstein-Barr virus (EBV) is also the most prevalent cause of infectious mononucleosis, also known as “the kissing disease.” The virus is a member of the herpes virus family, as indicated by the Centers for Disease Control and Prevention (CDC), a family of viruses that is also linked to cancer through human papillomavirus. Recently, a team of researchers in the United Kingdom has discovered the pathway through which the EBV can lead to certain blood cancers.

According to the CDC, most individuals will be infected with EBV at some point in their lifetime. The virus spreads primarily through saliva shared by kissing, shared food and drinks, shared eating utensils, and among children through drool on toys or surfaces. While many individuals with an EBV infection do not exhibit symptoms—particularly children—common signs include fatigue, fever, an inflamed throat, rash, and swelling in the lymph nodes, spleen, or liver. Symptoms usually pass within two to four weeks, though some cases can be more prolonged, with fatigue lasting up to several months.

Infectious mononucleosis, or “mono," can be caused by other viruses, but is most often brought on by EBV. With no vaccine available to prevent these illnesses, the best line of defense is prevention by avoiding kissing and sharing food or drinks with anyone who may have infectious mononucleosis.

In 1964, The Lancet published the first study showing that a virus can cause cancer. That virus came to be known as Epstein-Barr virus, named after the researchers who made the important finding. Included among the many EBV-related conditions are cancers such as Burkitt’s lymphoma, Hodgkin’s disease and non-Hodgkin’s lymphoma, and Nasopharyngeal carcinoma. Scientists have been researching the link between the virus and these cancers since the link between them was first discovered more than 50 years ago. Now, in the new study led by University of Sussex professor Michelle West, PhD, researchers have found how the virus works on a genetic level to drive the development of cancer. Their paper was recently published in the open-access journal eLIFE.

In their findings, the authors describe their investigation into how EBV controls the genes MYC and BCL2L11, essentially switching on the MYC gene to trigger development of lymphoma and switching off the BCL2L11 gene that causes cell death and stops lymphoma. Studying human B cells infected with EBV, the team observed how the virus works to reconfigure the DNA loops between MYC and BCL211 and their enhancers, which activate and increase the rate of transcription of a gene. They discovered that EBV works by essentially hijacking these enhancers and taking over the control centers that contact and regulate MYC and BCL211. The virus increases contact between a set of enhancers and the MYC gene to turn on that gene. At the same time, the researchers observed new enhancers of the BCL211 gene and found that the virus effectively blocks contact between them. They also found that with an available drug they can be used to reverse silencing of the BCL211 gene, which could offer an effective way to prevent EBV-related cancer.

“This is a key step towards uncovering how this common virus which, affects thousands of people every year, causes blood cancer,” said Dr. West in a press release issued by the University of Sussex. “It is now important to carry out further studies to determine how the Epstein-Barr virus controls other genes that are associated with lymphoma. This will tell us more about how the virus drives lymphoma development and will help to identify new ways of targeting Epstein-Barr virus-infected cancer cells with specific drugs.”

The study was made possible in part with funding from the UK blood cancer charity Bloodwise, which welcomed the findings as a sign of progress in tackling EBV-related cancers. “We have known for many years that the Epstein-Barr virus causes various types of lymphoma, but we were never sure of the exact mechanisms,” said Bloodwise Research Director Alasdair Rankin, PhD. “These new findings have shed light on how the virus is able to drive blood cancer development by altering the behavior of genes that control cancer growth. By mapping out the complex genetic interactions that help lymphoma cells grow and survive, this research can guide the design of new treatments to target the disease. It may also help to identify those drugs currently used to treat other diseases that could be effective in treating these types of lymphoma.”