Can the Epstein-Barr Virus Cause Autoimmune Illnesses?

In a study funded by the National Institute of Health, researchers have found reason to believe that infection with the Epstein-Barr virus (EBV), which results in the infectious mononucleosis, can cause the subsequent development of systemic lupus erythematosus and other chronic autoimmune illnesses.

While the mechanisms behind this association have been muddled, a novel computational method now shows that a viral protein found in EBV-infected human cells may activate genes associated with an increased risk for autoimmunity. Scientists supported by the National Institute of Allergy and Infectious Diseases are reporting their findings in the journal Nature Genetics.¹

Additionally, in the ongoing study being published Nature Genetics regarding transcription factors with EBV, research is also being done to see whether genetic analysis can further explain the relationship between EBV infection and Lupus. The study is being conducted by researchers led by John B. Harley, MD, PhD, director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s Hospital Medical Center, with his colleagues Matthew T. Weirauch, PhD, and Leah C. Kottyan, PhD, also of CAGE.

So far, researchers have found that EBNA2, a protein produced by the virus, and its related transcription factors activate some of the human genes associated with the risk for lupus and other autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease. Since EBV produces the protein EBNA2, it causes human proteins, known as transcription factors, to bind to areas of both the cell’s own genome and the virus’ genome. This action changes the expression of neighboring viral genes.

NIAID Director Anthony S. Fauci, MD, explained the significance of understanding the correlation between EBV and autoimmune diseases. “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. A better understanding of the complex causes of autoimmunity promises to lead to better treatment and prevention options.”²

Through a new computational and biochemical technique the team developed, which is known as the Regulatory Element Locus Intersection (RELI) algorithm, researchers are straining and comparing a large collection of genetic and protein data from healthy individuals and those with autoimmune diseases. With RELI, the team identified regulatory regions in genes associated with the risk of developing lupus that also bound EBNA2 and its related transcription factors. RELI also revealed in follow-up analyses that EBNA2 bound to genes associated with the risk for rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, celiac disease, and juvenile idiopathic arthritis.

Dr Harley stated his surprise with the team’s findings in the study. “We were surprised to see that nearly half of the locations on the human genome known to contribute to lupus risk were also binding sites for EBNA2. These findings suggest that EBV infection in cells can actually drive the activation of these genes and contribute to an individual’s risk of developing the disease.”

While researchers have noted the correlation between EBV and autoimmune diseases, they have also noted that other factors contribute the 7 autoimmune diseases mentioned above. Some individuals with activated regulatory genes associated with disease risk do not develop disease, and many of the regulatory genes that contribute to lupus and other autoimmune disorders that were analyzed in the study did not interact with EBNA2.

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References:

1. 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).
2. Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases. https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases. Accessed April 17, 2018.