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Epstein-Barr Virus and Autoimmune Diseases

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Autoimmune diseases are a set of complex body disorders with no clear pathological causes. Recently, many research studies have linked the Epstein Barr virus as a potential causative agent.

Before understanding the link between the Epstein Barr virus and autoimmune diseases, let’s have a brief introduction about these two entities.

 

the epstein barr virus and autoimmune diseases
the epstein barr virus and autoimmune diseases

Autoimmune Diseases:

An autoimmune disease is the one that causes the body’s immune system (that is meant to defend the body organs) to start attacking its own organs. The immune system is the defense force of body which protects it from various kinds of infections and diseases. Autoimmune diseases use inflammation as a weapon to wreak havoc with the body.

Therefore, it makes them unable to carry out their normal functions. Hashimoto’s thyroiditis was the first disease to be included in the autoimmune category. Some of the major autoimmune diseases include lupus, multiple sclerosis, celiac disease, inflammatory bowel disease, type 1 diabetes, juvenile arthritis, psoriasis and rheumatoid arthritis.

These diseases can involve any part of the body; skin, joints, muscles, blood and glands being the common target sites.

About 24 million Americans are affected by autoimmune diseases.

Till date, there is no satisfactory treatment for autoimmune diseases and they can exert severely debilitating effects in affected person.

Epstein Barr Virus:

Epstein-Barr virus (EBV) and Autoimmune Diseases
Epstein-Barr virus (EBV) and Autoimmune Diseases. Source: National Cancer Institute

Epstein Barr virus belongs to the herpes family of viruses and is strikingly common in humans. About 95% of the population is infected by this virus by the age of 20. It is famous for causing mononucleosis; also known as kissing disease.

This virus is transmitted by means of saliva or kissing hence named as kissing disease. Kissing disease is not fatal and tends to resolve on itself. The virus becomes dormant and stays in the body forever in a dormant stage.

However, its linkage with autoimmune disorders is really alarming due to the extremely common prevalence of Epstein Barr virus.

Can Epstein Barr virus really cause autoimmunity?

The answer to this multi-million question is yet to be found, unfortunately. After years of studies by many kinds of research, the answer can be given as ‘perhaps’ or ‘may be’. We have collected many hints that point towards EBV being the main culprit behind autoimmune disease but we still lack solid proof.

What is the basis of linking Epstein Barr virus with autoimmunity?

Here are a few reasons established by the hard work of many types of research:

  • Epidemiological studies show that about 85-90% of SLE (systemic lupus erythematosus) patients were seropositive for Epstein Barr virus. Since the infection rate is less in children so pediatric data was collected. It showed that EBV was positive in 91% of the SLE affected babies against the 70% prevalence in the control group. A similar study was conducted in patients of MS (multiple sclerosis) which is another common autoimmune disease. It was observed that MS was present in people who were positive for EBV. The incidence of MS was close to zero in serum-negative population. Epstein Barr virus seroconversion greatly raised the bar of getting multiple sclerosis later in life.

 

  • B lymphocytes or B cells are normally responsible for attacking the foreign intruders like viruses and bacteria and their number tends to decrease with advancing age. However, the number of B cells was unusually high in patients with autoimmune disorders like SLE. During the flare-up of SLE, there was a significant increase in the number of EBV- affected B cells. Studies have reported a 40% increase in Epstein Barr virus load in autoimmunity as compared to healthy individuals.

 

  • A certain protein produced by EBV, named as EBNA2, was documented to be present in the human genome in certain locations that are associated with autoimmunity.

How EBV does increase the risk of autoimmune diseases?

Epstein Barr virus has got a natural ability to dodge and manipulate our immune system. The picture of its tricky mechanism which alters the normal genomic sequence towards autoimmunity is still blurred.

Before moving ahead to understand the mechanism of EBV in easy words, it’s mandatory to mention the name of Dr. John Harley and his team here.

Dr. John Harley has produced the most advanced and authentic evidence on the link between EBV and Autoimmune diseases. He worked at Cincinnati medical Centre and set the foundation of understanding the role of EBV in autoimmunity.

As mentioned above, B lymphocytes are the main soldiers of our immune system that are trained to attack any foreign invaders like viruses and bacteria. B cells engulf that harmful agent and keep our body protected from hundreds of harmful microorganisms.

FBV attacks and gains the control of this main immune cell culminating in autoimmunity. After Epstein Barr virus gains control of B cell, it starts replicating freely in humans cells producing a protein named as EBNA2. This protein gets inserted in DNA (human genome) and changes the normal sequence to faulty ones.

A specific set pattern of coding or genes is responsible for cell growth and production of normal healthy proteins required for viability of cells. After getting infected by EBV, these faulty sequences further produce proteins known as variants (like lupus variants) which increase the risk of autoimmunity and work as a trigger.

During this process, EBV uses transcription factors as a switch. Transcriptions factors are signaling proteins that can activate or deactivate a gene sequence; hence can start or halt the production of resulting proteins.

Epstein Barr virus starts making its own transcription factors and keeps on producing faulty undesired proteins as a result.

The future of Autoimmunity and EBV:

Having a strong base of available shreds of evidence and the addition of the latest technology, we may have a breakthrough in the near future.

Cincinnati medical team has formulated new biochemical software that has a capacity of comparing large numbers of genomic data of autoimmune diseases with healthy individuals. This software is public and has been named as RELI (Regulatory Element Locus Intersection). The discovery of transcriptions factors has provided a direction to reach the conclusion.

Since we don’t have any cure for autoimmune diseases; researchers are striving to find preventive measures. The development of some vaccine against EBV that has the capacity to quarantine of limit the activity of virus will be huge prevention to avoid these agonizing autoimmune diseases.  

 

References:

  1. https://www.nih.gov/news-events/nih-research-matters/epstein-barr-virus-autoimmune-diseases
  2. https://www.cincinnatichildrens.org/news/release/2018/mono-virus
  3. Pohl D, Krone B, Rostasy K et al. High seroprevalence of Epstein–Barr virus in children with multiple sclerosis. Neurology 67(11), 2063–2065 (2006).
  4. 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).

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