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Epstein Barr (HHV-4) Links to Autoimmune Disease

The Epstein-Barr virus is a member of the herpes virus family – hence the designation HHV-4 – which also includes herpes simplex I and II, chicken pox virus (Varicella zoster, or VZV), and others.

Herpes viruses are generally quite adept at attacking and then retreating, sometimes lying dormant for weeks, months, years or even decades, before sometimes rearing their ugly heads in one form or another.

As many of you will already know, one of the prevailing current theories on the development of autoimmune disease involves an infectious trigger mechanism that sets autoimmune diseases in motion, at which point symptoms may appear.  Here we consider this line of thinking as it concerns a possible specific connection between Epstein-Barr and autoimmune conditions.

Are symptoms of Epstein-Barr similar to that of autoimmune conditions?

The first thing to understand is that not everyone who contracts Epstein-Barr/HHV-4 will present with symptoms.  In fact, a large proportion of people with the virus inside their bodies will never know it’s there or suffer from any real issues as a result of its presence.  That said, certain people, especially teenagers (who usually transmit this “kissing disease” via shared saliva of one form or another), can develop a clinical syndrome called infectious mononucleosis.

Another consideration is the fact that autoimmune diseases and their symptoms vary widely, depending on the condition being discussed.  So while Epstein-Barr infection may mimic symptoms of some autoimmune conditions, it may have nothing in common with others.

That said, one suspected autoimmune condition that shares several traits with Epstein-Barr virus/mononucleosis is chronic fatigue syndrome.

Both can manifest with fatigue, sore throat, swollen lymph nodes and generalized joint and muscular aches; but these findings may also indicate other viral illnesses, such as influenza.

And examination of patients’ blood has demonstrated increased antibodies to Epstein-Barr virus in those who are diagnosed with chronic fatigue syndrome, which is another indicator of a possible connection, and might explain the similarity of symptoms.

Are there any studies to connect Epstein-Barr/HHV-4 with later autoimmune onset?

Thus far, multiple sclerosis and lupus have been most closely linked to the virus.  Interestingly, while these findings predominate the literature, some researchers have actually found evidence suggesting the virus protects against lupus, further confusing the issue.

There is no lack of research and literature relating Epstein-Barr viral infections with later autoimmune disease of various types. However, as with so many disorders that have suspected infectious triggers, the current thinking is that such viral or bacterial triggers do not act alone, but must be combined with a genetic predisposition and/or genetic control to develop the conditions.  The nature of this complex interaction of multiple factors is unfortunately far from certain.

What are the reasons for any correlation or causation of mono and autoimmune onset?

Tough question.  The possibility of a causal connection has been under investigation since at least the early 1970s (and likely before), when an article published in The Lancet suggested a possible causative link.  Unfortunately, we still don’t know very much about the relationship between HHV-4 (or other viruses) and autoimmune disease, other than having a strong suspicion that the two are somehow linked.

This thinking is supported by multiple studies published in journals Clinical and Developmental Immunology and Cell Reports that have found apparent correlations between Epstein-Barr (and other viruses) and various autoimmune conditions.

The real challenge, as with so many correlated conditions, is collecting evidence that suggests more than just correlation, which hopefully leads to theories of causation.

In terms of the reasons that any correlations or causations might exist between the two, we are still woefully uncertain, and require more clarification on causative factors in order to be able to begin clarifying this connection.

However, in very general terms, we can say that a broad reason for the correlation and possible causal link involves the evidence from many studies and clinical observations that seems to suggest infectious triggers as a likely cause (or at least inciting factor) for a variety of autoimmune diseases.  Still, this leaves us with little specific information on the why and how of such connections, including that between Epstein-Barr virus and autoimmunity.  Fortunately, research continues today, in the hope of discovering further information that might explain more about this apparent connection.

Questions for your doctor:

  • How closely do you believe Epstein-Barr and autoimmunity are linked?  What other viruses could be connected to autoimmune disease?
  • Are there any tests or other diagnostic tools that might make such a connection between the two clearer?  If so, is there any real use for such tests, beyond academic purposes?
  • What are the best sources of information to learn more about these relationships?
  • Would antiviral treatments (assuming a viral trigger) do anything to relieve my autoimmune symptoms?
  • In addition to a rheumatologist, is it worth going to see an infectious disease specialist about this issue, considering there is strong evidence for an infectious link?

About the Author
Dr. Rothbard is a professional medical writer and consultant based in New York City, specializing in medical education articles targeted at a variety of audiences, from children through clinicians.  After leaving medicine, he worked as a biology and medical science educator for several years, before deciding to pursue writing full-time.  He may be reached at

This blog post was originally published by, written by Dr. Rothbard, and first published on Sep 5, 2014.

This post contains the opinions of the author. Autoimmune Association is not a medical practice and does not provide medical advice, diagnosis, or treatment. It is your responsibility to seek diagnosis, treatment, and advice from qualified providers based on your condition and particular circumstances. Autoimmune Association does not endorse nor recommend any products, practices, treatment methods, tests, physicians, service providers, procedures, clinical trials, opinions or information available on this website. Your use of the website is subject to our Privacy Policy.

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