At Cincinnati Children’s, researchers have made a remarkable discovery involving the virus that causes mono.
In a recently published study, scientists report the Epstein-Barr virus also increases the risks for some people of developing seven other major diseases.
The diseases include systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis, juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.
“This discovery is probably fundamental enough that it will spur many scientists around the world to reconsider the role of this virus in these disorders,” said John Harley, MD, PhD, director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s.
Dr. John Harley is the lead researcher and director of the Center for Autoimmune Genomics and Etiology.
He has devoted much of his career to studying lupus and a connection to the Epstein-Barr virus (EBV).
This most recent study shows that a protein produced by the virus, called EBNA-2, binds to multiple locations along the human genome that are associated with lupus and the six other diseases.
So environmental factors, such as viral or bacterial infections, poor diets, pollution, can interact with the human genetic blueprint and as a result influence the risk for disease.
“Now that we can do genomics that we couldn’t do 10 years ago, we asked the question well does the genomics of the virus interact with the host in a way that would be consistent with the possibility the virus might be causing the disease. So the answer to that so far is yes,” said Harley. “Not just for Lupus but all these other diseases too.”
The Cincinnati Children’s research team at CAGE looked at how EBV takes over. It’s a process that involves tiny proteins called transcription factors. These proteins constantly move along the strands of our DNA turning specific genes on and off to make sure cells function as expected.
“Before we’ve always thought about the transcription factors that regulate human gene expression being human which makes sense. But in this case, when this virus infects cells, it makes its own transcription factors and those sit on the human genome at Lupus risk variants and that’s what is increasing the risk for the disease,” said Leah Kottyna, PhD, an immunobiology expert with CAGE.
To closer analyze the synergy between disease genetics and the Epstein-Barr virus, Dr. Matthew Weirauch, a computational biologist and his team at CAGE gathered massive sets of genetic data. Then, researchers created two new algorithms analyzing every genetic change affecting the activity of the virus.
Through computer generated images, color blocks represent clusters of transcription factors. the more boxes filled in, the stronger the implications of the proteins in the disease.
“That is basically saying that this same cast of characters is a villain in multiple autoimmune diseases. They’re playing that role through different ways, and doing it at different places in your genome, but it’s the same sinister characters and so if we could develop therapies to stop them from doing this then it would help multiple diseases,” said Weirauch.
So far, no vaccine exists to prevent EBV infection. Researchers at CAGE hope their study will help expedite efforts that are currently underway.
At Cincinnati Children’s, the research team at CAGE is already taking next steps. Their findings have already uncovered potential leads for many other diseases, including breast cancer.
“The hope would be we could understand these disorders at a level that we could eliminate them. And so just the idea that scientific progress is entirely possible and we can make a difference and we can move things forward. This I hope turns out to be a small step in that direction,” said Harley.