Epstein-Barr Virus: A Key Player in Chronic Illness
by Dr. Bill Rawls
So, you’re experiencing symptoms of tiredness, achiness, sore throat, and possibly swollen lymph nodes and low-grade fever that just won’t go away.
You’ve Googled your symptoms, and mononucleosis pops up as a likely possibility. But if you’re well beyond college age, mononucleosis isn’t very common.
Chronic fatigue syndrome, fibromyalgia, and even Lyme disease are other possibilities you might have entertained, especially if you have symptoms beyond those mentioned above. But then you came across something called reactivated Epstein-Barr virus, which fits your symptoms to a tee.
If you are aware that Epstein-Barr virus (EBV) is the cause of mononucleosis, you may be wondering: What’s the difference between chronic reactivated EBV and mononucleosis? And beyond that, what makes chronic reactivated EBV chronic — and how does it play into other chronic illnesses?
To find out, read on to learn more about this complex and convoluted microbe called Epstein-Barr virus and what can make it a long-term troublemaker.
Almost Everyone Has EBV
Let’s start with the fact that EBV is much more common than you might imagine: >95% of world’s population has been infected with it.
Another interesting fact is that it’s a herpes-type virus. Yep, you read that right: EBV is a close relative of genital herpes. Known technically as Human Herpesvirus 4 (HHV-4), it’s #4 on the list of nine different herpes-type viruses that can infect humans.
Herpesviruses are composed of strands of DNA inside an envelope. After initial infection, they stay dormant in tissues indefinitely, but can reactivate if immune system functions become depressed.
In other words, if you’ve ever been infected with a herpesvirus like EBV, you will always carry it in your tissues.
EBV Can Spread Like Wildfire
The majority of people become infected with EBV as infants or young children. The virus spreads primarily by oral route via saliva. To enter the body, it infects mucous membranes lining the mouth, throat, and stomach. From there, the virus infects B cells, the type of white blood cell that produces antibodies. It also infects T cells and natural killer cells, but to a lesser extent. Infected white blood cells transport EBV throughout the body.
In this active phase, called the lytic phase, the virus takes over the machinery of infected cells to generate new viruses. This is when people are most symptomatic and contagious.
The virus spreads remarkably easily, especially in children. It is most typically spread by people who are infectious, but don’t know it — daycare workers, babysitters, grandmothers with big wet kisses. Following that, infected children rapidly pass it along to other children.
Which is a really good thing — because if you get it as an infant or young child (remember to thank your grandmother), you typically don’t get very sick at all. In fact, it’s unlikely that you would even remember the infection.
It’s only if you don’t get EBV at a young age and then get exposed later in life when your immune system is suppressed that you’re at risk for developing the form of EBV called mononucleosis.
Known as kissing disease, infectious mononucleosis (IM) is spread by intimate contact with someone shedding the virus. It typically occurs in young adults who haven’t been exposed early in life. It usually catches the person off guard when immune system functions are depressed, such as during the stress of high school or college.
Compared to EBV occurring in childhood, IM is much more severe: Common symptoms include sore throat, fever, severe fatigue, and swollen lymph nodes. It can drag on for months and be quite debilitating.25
Whether the initial encounter with EBV occurs as an innocuous infection as a child or as debilitating mononucleosis as a young adult, the host’s immune system eventually gains ground and the infection is contained.
The virus, however, is not eradicated. It persists inside memory B cells, a type of white blood cell that retains “memory” of an infection for future reference — except in this case, the cells are sabotaged into storing the actual virus. Memory B cells infected with EBV accumulate in lymphoid tissue and nerve tissue, and stay there for a lifetime.
This dormant state is referred to as the latent phase.9, 6, 12, 23Traditionally, people in the latent phase weren’t considered noninfectious. But with all the daycare workers, teachers, grandmas, and college students actively shedding the virus without knowing it, it’s become clear that someone can be very infectious without being ill. In fact, recent evidence supports that people often actively shed virus from tonsillar tissues without having significant symptoms.23
Either way, whether EBV is completely dormant or infectious without symptoms, the virus generally doesn’t cause any significant problems as long as immune system functions are robust. You can carry it for a whole lifetime and not know it — as most people do.
However, allow the immune system to become disrupted — by stress, poor diet, and other key factors I’ll explore below — and EBV can reactivate, causing symptoms similar to the mononucleosis, but much worse.4
Reactivated EBV Can Become Chronic
Chronic reactivated EBV is like mononucleosis from hell.
Symptoms of reactivated EBV include severe chronic fatigue, chronic achiness, chronic sore throat and irritation of mucous membranes, swollen lymph nodes, and a range of debilitating neurological symptoms. Symptoms can wax and wane for years. Severe cases can include evidence of liver dysfunction, immune suppression, and anemia.1
The most plausible explanation for why chronic reactivated EBV is so severe and unrelenting is that it’s not just EBV that’s at play.
This is where things get both interesting and complicated.
People often carry other herpesviruses in addition to EBV. The list includes Herpes simplex types 1 and 2 (oral and genital herpes), varicella-zoster virus (causing both chickenpox and shingles), cytomegalovirus (CMV), HHV-6 types a and b, HHV-7, and HHV-8.
Though they are all related, each of these viruses infects the body in a different way — therefore they cause slightly different symptom profiles. In important ways, they are all are remarkably common:
They stay dormant in tissues and can be reactivated just like EBV.
If disruption of a person’s immune functions allows reactivation of multiple herpesviruses at once, symptoms can be severe and highly variable.
But that isn’t the end of the story.
Many people with chronic Lyme disease, fibromyalgia, and chronic fatigue syndrome are found to have reactivation of EBV, along with other herpesviruses and a list of other microbes including Mycoplasma, Bartonella, Chlamydia, and new microbes added to the list every day.
This strongly suggests that reactivation of EBV is likely not EBV alone.
The Connections Between EBV and Chronic Illnesses Are Many
Scientists are just beginning to explore the link between chronic EBV and other chronic illnesses, but one of the most well-researched is EBV’s relationship with multiple sclerosis (MS). Many studies have defined a variety of different mechanisms by which the virus could initiate and perpetuate MS — not enough to define EBV as the sole cause of MS, but highly suggestive that it does play a role in the illness.10
Similarly, studies have shown high viral loads of active EBV in a high proportion of patients with a variety of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, and autoimmune thyroiditis.14 Again, a strong link, but not enough to suggest absolute cause of EBV alone.
And that’s not the end of the multi-microbe connections.
Recent evidence has suggested that EBV and HHV-6a might together play a role in MS.29 MS has also been linked to a variety of different microbes including, but not limited to, Chlamydia pneumoniae,35, 37 Mycoplasma sp., Spherula insularis, and paramyxovirus.14, 36
Autoimmune diseases have also been linked to a variety of microbes, including EBV, but also additional herpesviruses; other viruses including Parvovirus; a protozoan called Toxoplasmosis; and bacteria including Mycoplasma, Yersinia, and others commonly associated with chronic Lyme disease.14
Often referred to as stealth pathogens, the microbes mentioned and many others share similar stealthy characteristics:
- They have the ability to live inside cells.
- They infect white blood cells and are carried throughout the body, especially to areas of inflammation.
- They can persist in a dormant state.
- They are master manipulators of the immune system.
- They can exist in healthy people without causing illness.
- They are present in all populations of the world.
The deeper you dig, the more connections you find between chronic illnesses and stealth microbes. But after a while, you begin to appreciate that it’s not as much the microbes causing problems as it is disruption of the host’s immune functions that allows those microbes to flourish.
In other words, a person could be harboring a variety of stealth microbes — EBV, CMV, HHV-7, Borrelia, Bartonella, Mycoplasma, Chlamydia, and others — and not be ill as long as their immune system functions are robust.
Let immune system functions falter, however, and like a pot boiling over on the stove, the microbes erupt and cause illness.
Chronic Immune Dysfunction Is Triggered by the Perfect Storm
I came to see chronic illness differently than most other physicians because of my personal struggle overcoming chronic Lyme disease.
My experience taught me that the microbes are always there — I had likely harbored mine since childhood. It’s not until a perfect storm of factors comes together to disrupt immune functions that a person becomes ill. For me, that perfect storm was caused primarily by years of chronic sleep deprivation associated with every-other-night obstetrics on-call-duty and eating a poor diet on the run, but there were other minor stress factors as well.
My recovery did not progress until I started addressing the underlying chronic immune dysfunction.
As I shifted my practice toward caring for individuals with chronic illness, I began to see similar patterns in my patients — not necessarily the same stress factors that I had experienced, but stress factors that disrupt immune functions just the same. I began cataloging them and, interestingly, I reached a limit of just 7 categories of stress factors that are associated with chronic illness.
As astounding as it may sound, I came to the conclusion that the causes of all chronic illnesses can be traced back to these 7 factors that I came to call System Disruptors. I’ve been testing this theory for more than 10 years and always find it to be reliable. I’ve also discovered solid scientific support for my theory.
The 7 System Disruptors are:
1. Poor diet. We live in a world saturated with artificially manipulated foods. Regular consumption of these foods disrupts all systems of the body.
2. Toxins. The modern world is saturated with artificial toxins. Toxins disrupt all healing systems of the body.
3. Emotional stress. Continually running from the proverbial tiger inhibits digestion, suppresses immune function, disrupts sleep, and sets the stage for chronic illness.
4. Physical stress. Cumulative trauma, excessive heat or cold causes damage to the body, but living a sedentary life can be just as harmful.
5. Oxidative stress. Every cell in the body is continually generating free radicals as a byproduct of energy production. Free radicals damage internal components of cells. Inflammation is also a type of free radical damage.
6. Artificial radiation. Normal background radiation from the sun, solar system, and the earth itself are now amplified sources of radiation that saturate the modern world.
7. Microbes. The effects from this system disruptor set the stage for chronic illness.
For every patient with chronic illness, I can always trace back to a perfect storm of factors that came together to cause the person’s illness. What type of chronic illness they ended up with depends on three factors:
- The person’s genetics — which determines risk, but not whether an illness will occur
- The variety of different low-grade stealth pathogens the person has collected through life
- How System Disruptors contribute to immune dysfunction, which allows low grade pathogens with stealthy characteristics to flourish and upset the balance of the microbiome and homeostasis in the body
Diagnosing and Treating Chronic EBV Isn’t Black and White
To help identify chronic EBV, start by trying to rule out infectious mononucleosis. By definition, IM is an acute infection with EBV alone, and there are antiviral agents (such as acyclovir, ganciclovir, and vidarabine) that work extremely well for IM and other acute infections of herpes-type viruses, so it’s worth doing testing to define IM over reactivated EBV.
Testing for IM looks for antibodies to the virus; the presence of different types of antibodies can distinguish between IM and reactivated EBV. But testing for IM isn’t always straight-forward — mononucleosis-like syndromes can also occur with other herpesviruses (CMV, HHV-6), other viruses (typically adenoviruses), and a protozoan called Toxoplasma gondii.26 In other words, many different viruses can cause viral syndromes similar to EBV.
If you have all the symptoms of chronic reactivated EBV, then the likelihood of EBV being present is quite high, along with other microbes.
As for treating chronic reactivated EBV, because there are antiviral agents that work well for IM, you might expect that chronic EBV would also respond to antivirals.
Unfortunately, antivirals don’t work for chronic EBV.
Scientists have sorted out the technical reason for this. Antiviral agents work by blocking DNA polymerase, an enzyme the virus uses to replicate inside cells. Latent or chronic EBV infection, however, does not require DNA polymerase for the virus to replicate — therefore, current antiviral agents are ineffective against chronic EBV infection.1
Other conventional therapies, including steroid therapy (prednisone) and immunosuppressive drugs, have been used to treat chronic EBV infection, but success has been limited.1These therapies can inhibit the destructive processes of a disrupted immune function, but they have no capacity to restore normal immune function.
Lots of researchers are also looking at vaccines against EBV. The problem is that characteristics of the virus vary greatly across different geographical areas, making it difficult to create a single vaccine.8
Other methods of eradicating EBV being contemplated by conventional medical science include: B-cell depletion with monoclonal antibodies (targeting EBV-infected B cells with immunoglobulins) and new types of antiviral drugs.11, 16, 20
Focusing all efforts on eradicating EBV, however, is short-sighted. The bottom line: The underlying problem is chronic immune dysfunction, and you will not start getting well until normal immune system functions are restored.
There’s A More Practical Approach to Regaining Wellness
Remember, EBV doesn’t cause problems unless immune system functions have been disrupted.1, 14, 20, 23 Therefore, any solution must address restoring normal immune system functions in order to suppress whatever microbes may be present and flourishing.
First and foremost is minimizing the 7 System Disruptors. Following an optimal diet and making some lifestyle modifications to promote a healing environment in the body is essential for overcoming chronic EBV or any other chronic illness.
Modern herbal therapy should be the cornerstone of any restorative approach. Herbal extracts have incredible abilities, including:
- Reducing destructive inflammation
- Enhancing natural killer cells and other aspects of the immune system necessary to control microbes like EBV
- Balancing hormone systems in the body that have been disrupted by chronic illness
- Suppressing stealth microbes directly to restore balance in the microbiome
While many herbs have been found to suppress EBV, EBV is rarely found in isolation — chronic immune dysfunction always allows a variety of low-grade stealth pathogens to flourish. Therefore, a comprehensive regimen of herbal extracts is necessary.
Some effective herbal extracts for restoring immune function, balancing the microbiome, and suppressing viruses such as EBV include:
Generally most people will respond to restorative solutions alone. Drug therapy is only necessary if severe or extreme illness is not responding to the restorative therapies. It is, however, important to maintain an ongoing working relationship with your medical provider during your entire recovery.
Ultimately, all of this is great news for those with chronic reactivated EBV: It means the power to take back control of your health and feel better is in your hands. By learning how to limit the System Disruptors in your life, you’ll start to strengthen your immune function so you can live in harmony with microbes like EBV.
Unfortunately, I had to learn about this through my daughter who had severe EBV that lingered and ultimately led to the removal of her tonsils as well as using LDI/LDA therapy: https://madisonarealymesupportgroup.com/2016/05/30/new-kids-on-the-block-ldaldi/
Being in Wisconsin, an epicenter for Lyme, our LLMD is also who we take our children to – just in case, God forbid, they should become infected. Our LLMD believes, as Dr. Rawls, that immunoconfusion, or a perfect storm of events overwhelming the immune system, is behind many chronic diseases. Retraining the immune system to recognize friend vs foe is behind LDA/LDI treatment and can often help many chronic conditions. It certainly has helped my daughter, who is also hypothyroid, hypoglycemic, and suffers from severe endometriosis. EBV nearly destroyed her liver.
I can attest to having to learn the importance of diet, hormones, stress, environmental toxins, and microbes. It is crucial to find a practitioner(s) who is versed in this approach to tease out your imbalances through proper testing and clinical diagnosis. As with Lyme, much testing isn’t helpful and requires an experienced eye and listening ear to help you uncover your personal pitfalls. Most doctors are not trained in hormone therapy and with the chemically laden environment we live in, this is most unfortunate as many suffer from serious hormonal imbalances and mineral/vitamin deficiencies. Doctors are taught to fear hormones when they are naturally occurring substances in the body that often need supplementing due to environmental factors. I’m of course advocating for bioidential hormones – as close to nature as possible; however, for those of you suffering with endometriosis that makes your life unbearable, please read this unique approach which gave my daughter her life back: https://www.theendocure.com/
1. Cohen J. Optimal Treatment for Chronic Active Epstein-Barr Virus Disease. Pediatr Transplant. 2009 Jun; 13(4): 393–396.
2. Joo E et al. An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis. Korean J Intern Med. 2011 Dec; 26(4): 466–469.
3. Kang M, Kief E. Epstein–Barr virus latent genes. Exp Mol Med. 2015 Jan; 47(1): e131.
4. Jha H, Pei Y, Robertson E. Epstein–Barr Virus: Diseases Linked to Infection and Transformation. Front Microbiol. 2016; 7: 1602.
5. Tsao S et al. The role of Epstein–Barr virus in epithelial malignancies. J Pathol. 2015 Jan; 235(2): 323–333.
6. Paschale M and Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World J Virol. 2012 Feb 12; 1(1): 31–43.
7. Shen Y et al. Understanding the interplay between host immunity and Epstein-Barr virus in NPC patients. Emerg Microbes Infect. 2015 Mar; 4(3): e20.
8. Tzellos S and Farrell P. Epstein-Barr Virus Sequence Variation—Biology and Disease. Pathogens. 2012 Dec; 1(2): 156–175.
9. Iizasa H et al. Epstein-Barr Virus (EBV)-associated Gastric Carcinoma. Viruses. 2012 Dec; 4(12): 3420–3439.
10. Lassmann H et al. Epstein–Barr virus in the multiple sclerosis brain: a controversial issue—report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria. Brain. 2011 Sep; 134(9): 2772–2786.
11. Pender M and Burrows S. Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clin Transl Immunology. 2014 Oct; 3(10): e27.
12. Stanfield B and Luftig M. Recent advances in understanding Epstein-Barr virus. Version 1. F1000Res. 2017; 6: 386.
13. Gru A et al. The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment. Curr Hematol Malig Rep. 2015 Dec; 10(4): 456–467.
14. Lossius A et al. Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation. Viruses. 2012 Dec; 4(12): 3701–3730.
15. Rowe M, Fitzsimmons L, and Bell A. Epstein-Barr virus and Burkitt lymphoma. Chin J Cancer. 2014 Dec; 33(12): 609–619.
16. Martorelli D et al. Exploiting the Interplay between Innate and Adaptive Immunity to Improve Immunotherapeutic Strategies for Epstein-Barr-Virus-Driven Disorders. Clin Dev Immunol. 2012; 2012: 931952.
17. Houldcroft C and Kellam P. Host genetics of Epstein–Barr virus infection, latency and disease. Rev Med Virol. 2015 Mar; 25(2): 71–84.
18. Draborg AH, Duus K, and Houen G. Epstein-Barr Virus in Systemic Autoimmune Diseases. Clin Dev Immunol. 2013; 2013: 535738.
19. Rac J et al. Telomerase Activity Impacts on Epstein-Barr Virus Infection of AGS Cells. PLoS One. 2015; 10(4): e0123645.
20. Pender M. The Essential Role of Epstein-Barr Virus in the Pathogenesis of Multiple Sclerosis. Neuroscientist. 2011 Aug; 17(4): 351–367.
21. Dittfeld A et al. A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders. Cent Eur J Immunol. 2016; 41(3): 297–301.
22. Chen XZ et al. Epstein–Barr Virus Infection and Gastric Cancer
A Systematic Review. Medicine (Baltimore). 2015 May; 94(20): e792.
23. David A. Thorley-Lawson. EBV Persistence—Introducing the Virus. Curr Top Microbiol Immunol. 2015; 390(Pt 1): 151–209.
24. Iwakiri D. Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis. Cancers (Basel). 2014 Sep; 6(3): 1615–1630.
25. Dunmire SK, Hogquist KA, and Balfour HH. Infectious Mononucleosis. Curr Top Microbiol Immunol. 2015; 390: 211–240.
26. Krupka JA et al. Infectious mononucleosis-like syndrome with high lymphocytosis and positive IgM EBV and CMV antibodies in a three-year-old girl. Cent Eur J Immunol. 2017;42(2):210-212.
27. Collin V, Flamand L. HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomally Integrated HHV-6A/B. Viruses. 2017 Jun 26;9(7).
28. Warren-Gash C et al. Association between human herpesvirus infections and dementia or mild cognitive impairment: a systematic review protocol. BMJ Open. 2017 Jun 23;7(6):e016522.
29. Fierz W. Multiple sclerosis: an example of pathogenic viral interaction? Virol J. 2017 Feb 28;14(1):42.
30.Enquist LW, Leib DA. Intrinsic and Innate Defenses of Neurons: Détente with the Herpesviruses. J Virol. 2016 Dec 16;91(1).
31. Hutt-Fletcher LM. The Long and Complicated Relationship between Epstein-Barr Virus and Epithelial Cells. J Virol. 2016 Dec 16;91(1).
32. Siddiquey MN et al. Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma. Cancer Sci. 2014 Jun;105(6):713-22.
33. Cekanaviciute E et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 2017 Sep 11. pii: 201711235.
34. Berer K et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017 Sep 11. pii: 201711233.
35. Ivanova MV et al. Role of Chlamydia in Multiple Sclerosis. Bull Exp Biol Med. 2015 Sep;159(5):646-8.
36. Libbey JE, Cusick MF, Fujinami RS. Role of pathogens in multiple sclerosis. Int Rev Immunol. 2014 Jul-Aug;33(4):266-83.
37. Sriram S et al. Detection of chlamydial bodies and antigens in the central nervous system of patients with multiple sclerosis. J Infect Dis. 2005 Oct 1;192(7):1219-28. Epub 2005 Sep 2.
38. Buhner S. Herbal Antivirals, Natural Remedies for Emerging & Resistant Viral Infections. Storey Publishing. Copyright 2013.