Development of systemic lupus erythematosus (SLE) and other chronic autoimmune illnesses has been linked to Epstein-Barr virus (EBV) infection, the cause of infectious mononucleosis.
The mechanism, however, is still not clear. A viral protein found in EBV-infected human cells may activate genes associated with increased risk for autoimmunity, as shown by a novel computational method.National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, M.D said “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.”
Worldwide, EBV infection is pervading human population. Childhood is when most people procure EBV, and they experience no symptoms or only a short, mild cold-like illness, and remain infected throughout their lives while remaining asymptomatic. A syndrome of infectious mononucleosis characterized by prolonged fever, sore throat, swollen lymph nodes and fatigue, occurs when an adolescent or young adult is infected with EBV for the first time. Infectious mononucleosis is also called “mono” or the “kissing disease,” generally resolves with rest and only rarely causes serious complications.
When EBV infects human immune cells, EBNA2 – a protein that is produced by the virus – recruits human proteins (transcription factors) to bind to regions of both the EBV genome and the cell’s own genome. As a result, EBNA2 along with the human transcription factors change the expression of neighboring viral genes.
EBV is a risk factor for development of Systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis, inflammatory bowel disease (IBS), type 1 diabetes, juvenile idiopathic arthritis and celiac disease.
In the latest study, researchers discovered that EBNA2 and its related transcription factors activate some of the human genes associated with the risk of development of Systemic lupus erythematosus (SLE) and several other autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis, inflammatory bowel disease (IBS), type 1 diabetes, juvenile idiopathic arthritis and celiac disease.
EBV infection may result in autoimmune diseases, particularly Systemic lupus erythematosus (SLE), as proposed in previous studies. In the present-day work, research led by John B. Harley, M.D., Ph.D., director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s Hospital Medical Center, with his colleagues Matthew T. Weirauch, Ph.D., and Leah C. Kottyan, Ph.D., also of CAGE, wondered whether genetic analysis could further, explain the association between EBV infection and Systemic lupus erythematosus (SLE). A new computational and biochemical technique known as the Regulatory Element Locus Intersection algorithm, or RELI, was developed by their team; comparing a large
collection of genetic and protein data from healthy individuals and those with autoimmune diseases. The team used RELI to identify regulatory regions in genes associated with the risk of developing Systemic lupus erythematosus (SLE), which also bound EBNA2 and its related transcription factors.
“We were surprised to see that nearly half of the locations on the human genome known to contribute to Systemic lupus erythematosus (SLE) risk were also binding sites for EBNA2,” said Dr. Harley. “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.”
Investigators used RELI to probe regulatory genes associated with other autoimmune diseases and found that EBNA2 bound to genes associated with the risk for multiple sclerosis, inflammatory bowel disease, juvenile idiopathic arthritis, rheumatoid arthritis, type 1 diabetes and celiac disease during a follow-up analysis.
Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology, and Transplantation at NIAID announced “Because EBV is most often encountered in early childhood, avoiding infection is practically impossible … 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.”
Development of the seven autoimmune conditions discussed in the paper so far is noted to be influenced by other factors and not only the EBV infection as noted by researchers. Most of the regulatory genes that add to Systemic lupus erythematosus (SLE) and other autoimmune disorders did not interact with EBNA2. Furthermore, a number of individuals with activated regulatory genes associated with disease risk factor do not develop the disease.
To study the underlying causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses, research conducted and supported throughout the United States, and worldwide by NIAID at NIH.
Researchers and organizations in the study of the EBV virus and how it works deserves some accolade, as they’ve put in so much effort to study and help out with the cause, nature and other factors that are responsible for the cause of the development of these seven autoimmune conditions.