![]() The Cincinnati Children’s team suspects that the EBNA2 transcription factor from EBV is helping change how infected B cells operate, and how the body responds to those infected cells. However, when the transcription factors change what they do, the normal functions of the cell can also change, and that can lead to disease. These proteins constantly move along the strands of our DNA, turning specific genes on and off to make sure cells function as expected. ![]() Each cell uses a subset of these to become what they are and to respond to their environment. Our bodies have about 1,600 known transcription factors at work within our genome. The Cincinnati Children’s research team has discovered a new clue about how the virus does this, a process that involves tiny proteins called transcription factors. The EBV virus invades the B cells themselves, re-programs them, and takes over control of their functions. However, when EBV infections occur, something unusual happens. When viral and bacterial infections strike, our bodies respond by commanding B cells within our immune systems to crank out antibodies to battle the invaders. I think this study might well encourage them to push forward faster and with rededicated effort.” How EBV hijacks our immune system “Some EBV vaccines are under development. “I think we’ve come up with a really strong rationale for encouraging people to come up with more of an effort,” Kottyan says. So far, no vaccine exists that will prevent EBV infection. “As a consequence, and assuming that others can replicate our findings, that could lead to therapies, ways of prevention, and ways of anticipating disease that don’t now exist.” “This discovery is probably fundamental enough that it will spur many other scientists around the world to reconsider this virus in these disorders,” Harley says. Today’s study adds weight to those lupus findings and adds six more well-known diseases to the list. That work includes proposing mechanisms that the immune system uses in response to the virus that lead to lupus, and showing that children with lupus almost always are infected with EBV. Harley, who has devoted much of his career to studying lupus, found possible connections between lupus and EBV years ago. Over the years, scientists have linked EBV to a few other rare conditions, including certain cancers of the lymphatic system. Mono was nicknamed the “kissing disease” years ago because the virus spreads primarily via contact with saliva. Mononucleosis, which causes weeks of extreme fatigue, is the most common illness caused by EBV. Once infected, the virus remains in people for their entire lives. In less-developed nations, 90 percent of people become infected by age 2. and other developed nations, more than 90 percent of the population becomes infected by age 20. Here are some of the initial implications: New concern about the ‘kissing disease’ĮBV is a strikingly common virus. The full impact of this study could take years to explore. “And not just for lupus, but all these other diseases, too.” “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,” Harley says. Overall, the study 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. The study shows that a protein produced by the Epstein-Barr virus, called EBNA2, binds to multiple locations along the human genome that are associated with these seven diseases. Critical contributions were provided by Xiaoting Chen, PhD, and Mario Pujato, PhD, both also in CAGE. The project was led by three scientists: John Harley, MD, PhD, Director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s and a faculty member of the Cincinnati VA Medical Center Leah Kottyan, PhD, an immunobiology expert with CAGE and Matthew Weirauch, PhD, a computational biologist with the center. Study results were published today in the journal Nature Genetics. Combined, these seven diseases affect nearly 8 million people in the U.S. Those diseases are: systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes. A far-reaching study conducted by scientists at Cincinnati Children’s reports that the Epstein-Barr virus (EBV)-best known for causing mononucleosis-also increases the risks for some people of developing seven other major diseases.
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