Infection with Epstein-Barr virus (EBV), the cause of infectious mononucleosis, has been associated with subsequent development a number of chronic autoimmune illnesses, but the mechanisms behind this association have been unclear. Now, experts have reported that a viral protein found in EBV-infected human cells may activate genes associated with increased risk for autoimmunity.
“Many cases of autoimmune illness are difficult to treat and can result in debilitating symptoms. Studies like this are allowing us to untangle environmental and genetic factors that may cause the body’s immune system to attack its own tissues,” said NIAID Director Anthony S. Fauci, M.D. “A better understanding of the complex causes of autoimmunity promises to lead to better treatment and prevention options.”
EBV infection is nearly ubiquitous in the human population worldwide. Most people acquire EBV in early childhood, experience no symptoms or only a brief, mild cold-like illness, and remain infected throughout their lives while remaining asymptomatic. When infection first occurs in adolescence or young adulthood, EBV can lead to a syndrome of infectious mononucleosis characterized by prolonged fever, sore throat, swollen lymph nodes and fatigue. This syndrome, also known as “mono” or the “kissing disease,” generally resolves with rest and only rarely causes serious complications.
When EBV infects human immune cells, a protein produced by the virus—EBNA2—recruits human proteins called transcription factors to bind to regions of both the EBV genome and the cell’s own genome. Together, EBNA2 and the human transcription factors change the expression of neighboring viral genes.
In the current study, the researchers found that EBNA2 activates some of the human genes associated with the risk for several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, and celiac disease.
“Because EBV is most often encountered in early childhood, avoiding infection is practically impossible,” said Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID. “However, now that we understand how EBV infection may contribute to autoimmune diseases in some people, researchers may be able to develop therapies that interrupt or reverse this process.”
Reference: J Harley, et al. Transcription factors operate across disease loci, with EBNA2 implicated in immunity. Nature Genetics DOI: 10.1038/s41588-018-0102-3 (2018).