autoimmune disease
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A new study explains how Epstein-Barr virus infections can lead to autoimmune diseases such as rheumatoid arthritis, mononucleosis, or lupus.

Approximately 90% of Americans have been infected with Epstein-Barr virus (EBV), which can cause infectious mononucleosis, more commonly known as mono. There has been scientific evidence that EBV is also linked to multiple autoimmune disorders, such as lupus (systemic lupus erythematosus). Notably, an EBV infection in children can raise the risk of lupus as much as 50-fold in children. However, there is a lack of sufficient studies to explain this phenomenon at the molecular level.

Previous studies have shown the existence of over 50 areas in the genome where genetic changes were associated with lupus; these areas are known as risk loci. A group from the Cincinnati Children’s Hospital Medical Center in Ohio, United States questioned whether proteins produced as a result of an EBV infection can bind and interact with the risk loci for lupus. Their study was recently published in the journal Nature Genetics.

EBNA2 and its role in multiple autoimmune diseases

Using computational analyses, the authors of this study identified strong associations between an EBV gene product, called EBNA2, and lupus risk loci. They found that over half of the loci were predicted to have some interaction with EBNA2.

The group also investigated other autoimmune diseases and found that EBNA2 also increases the risk of developing six other immune diseases: multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis, and celiac disease.

Their analyses showed that many EBNA2-related transcription factors that are naturally involved in inflammation pathways also bind to risk loci associated with autoimmune diseases.

Implications of new computational methods in the study

The results of this study highlight certain proteins and factors that may play significant roles in several autoimmune diseases. These proteins and factors can act as a blueprint for future studies to develop strategies to target the outlined potential mechanisms to treat autoimmunity.

The work by this group has furthered our understanding of how viral infections can influence the genetic risk of seemingly unrelated diseases. Furthermore, their new computational approaches to analyze genomic and biological data can be applied to many different diseases and can hopefully shed light on other potential gene-environment interactions.

Written by Branson Chen, BHSc

Reference: Harley JB, Chen X, Pujato M, Miller D, Maddox A, Forney C, Magnusen AF, Lynch A, Chetal K, Yukawa M, Barski A. Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nature Genetics. 2018 Apr 16:1.

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