Virus linked to serious conditions
New research suggests the virus that causes glandular fever also increases the risks of developing seven other major diseases.
A US study has found that a protein produced by the Epstein-Barr virus, called EBNA2, binds to multiple locations along the human genome that are associated with the following seven diseases - systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease.
The study results have been published in the journal Nature Genetics.
Overall, the finding sheds new light on how environmental factors, such as viral or bacterial infections, poor diet, pollution or other hazardous exposures, can interact with the human genetic blueprint and have disease-influencing consequences.
“Now, using genomic methods that were not available 10 years ago, it appears that components made by the virus interact with human DNA in the places where the genetic risk of disease is increased,” says research leader Dr John Harley.
“And not just for lupus, but all these other diseases, too.”
It remains unclear how many cases of the seven diseases listed in the study can be traced to prior EBV infection. More genomic analyses involving many more patients with these diseases will be required to make reliable estimates.
“The impact of the virus is likely to vary across the diseases,” Dr Harley says.
“In lupus and MS, for example, the virus could account for a large percentage of those cases. We do not have a sense of the proportion in which the virus could be important in the other EBNA2-associated diseases.”
However, the breakthrough identification of specific transcription factors connected to EBV infections opens new lines of study that could accelerate efforts to find cures.
“This same cast of characters is a villain in multiple immune-related diseases,” says computational biologist Dr Matthew Weirauch.
“They’re playing that role through different ways, and doing it at different places in your genome, but it’s the same sinister characters. So if we could develop therapies to stop them from doing this, then it would help multiple diseases.”
A number of compounds—some experimental, some approved as medications for other conditions—already are known to be capable of blocking some of the high-risk transcription factors listed in the paper, Dr Weirauch says.
While the EBV-related findings involved more than 60 human proteins linked to seven diseases, the research team has also applied the same analytic techniques to tease out connections between all 1,600 known transcription factors and the known gene variants associated with more than 200 diseases.
The results of that massive cross-analysis also appear in the new study, documenting intriguing associations involving 94 conditions.
“Our study has uncovered potential leads for many other diseases, including breast cancer,” Dr Harley says.
“We cannot possibly follow up on all of these, but we are hoping that other scientists will.”
After decades of research to hunting down the causes of lupus, Dr Harley says this study represents the most important discovery of his career.
“I’ve been a co-author in almost 500 papers. This one is more important than all of the rest put together. It is a capstone to a career in medical research,” he says.