Epstein-Barr virus (EBV) is a virus found in the saliva glands that is the direct cause of mononucleosis (better known as mono or the “kissing disease”). Many people (~90%) have the virus, although most never develop mono or any unwanted symptoms. There are a few ways that EBV relates to autoimmunity and related disorders, however. Read on to learn about these relations and how you can help keep EBV controlled and dormant in your system.

How EBV Causes Autoimmune Disorders

CD8 Reduced

CD8+ T-cells are a kind of cell that inhibits viruses.

The deficiency of these cells is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves’ disease, Hashimoto’s thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia [1].

Some scientists believe that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by not controlling Epstein-Barr virus (EBV) infection [1].

If EBV isn’t controlled, it can wreak havoc on the body. When EBV infects B cells, it can make them “autoreactive,” which means its products (antibodies) target our own tissues [1].

According to this hypothesis, autoimmunity occurs in the following steps [1]:

  1. CD8+ T-cell deficiency – This is genetic
  2. EBV infection and proliferation of EBV because of CD8+ T-cell deficiency
  3. Increased antibodies against EBV (kind of like the second line of defense)
  4. EBV infects a specific organ, and particularly B Cells in that organ. This corrupts the B cells to attack our own tissue. One theory is that since viruses and bacteria have proteins similar to our own proteins, we mistakenly attack our own proteins. This confusion by our immune system is called molecular mimicry
  5. B cells proliferate in the infected organ
  6. T cells are drawn into the organ and also attack our tissue
  7. Development of ‘structures’ in the target organ, which causes B cells to attack our tissues (dependent on Th17 cells) [2]

Important Factors That Influence CD8+ Cells

As we age, CD8+ cells go down, which is one reason why autoimmunity goes up as we age [1].

Estrogen also decreases CD8+ T cells, which explains the higher incidence of autoimmunity in females [1].

Sunlight/vitamin D is very important for CD8+ T cell production, which explains why countries that get less sunlight have a higher occurrence of autoimmunity [1].

Acute stress actually increases CD8+ T cells, but chronic stress doesn’t affect it [3, 4].

However, chronic stress can cause reactivation of EBV, likely by downgrading the Th1 immune response [5].

How EBV and Viral Infections Cause Low Pregnenolone Levels

I see it often being the case that after prolonged stress, pregnenolone levels dip and synthesis of downstream hormones decline.

Pregnenolone is the mother of all hormones and is a neurosteroid. The most obvious explanation is because cortisol is ‘stealing’ or diverting pregnenolone for cortisol production and depleting it. When pregnenolone is depleted, there will be less of it to produce future cortisol production.

However, there’s another possible contributing factor.

When you’re under high stress the body releases cortisol, which decreases your immune system.

Specifically, the Th1 immune system is suppressed by chronic stress [4].

This aspect of the immune system (Th1) protects us from viral reactivation.

When this arm of the immune system is suppressed, viral infections can then reactivate – including EBV, herpes, and a host of other viruses.

When a viral infection becomes active, it “hijacks” what’s known as the “mevalonate pathway.” Viruses use this pathway to make their protective outer coats.

In response, your body makes interferon, which suppresses the mevalonate pathway, which in turn suppresses the virus. However, inhibiting this pathway leads to a reduction in the synthesis of pregnenolone and CoQ10.

Perhaps the most common virus that causes this pathway to be inhibited is Epstein-Barr Virus (EBV). Over 90% of the population eventually gets this virus.

Read “Host Defense against Viral Infection Involves Interferon-Mediated Down-Regulation of Sterol Biosynthesis.”

Acute infections respond well to this, as the interferon production is helpful in the short term. But in the long term, this can lead to starving your body of CoQ10 and key hormones. This appears to be part of what happens in CFS.

I was deficient in pregnenolone, even when I lowered my stress and I never understood why. It’s possible that by me having a Th1 dominant system, I produce higher levels of interferon, which suppressed the pathway that produces pregnenolone.

Red yeast rice/statins mildly block the same pathway and can actually have a mild antiviral effect at a low dose and a strong effect at a high dose.

Supplements that increase your Th1 system will indirectly prevent EBV reactivation.

Checking Your Pregnenolone Levels

You can request that your doctor test your pregnenolone. Conventional doctors will look at high or low pregnenolone levels and not mention anything. Sometimes, a lab result may be in the reference range, but not actually be in the optimal range. Reference ranges are not the same as optimal ranges. This is why even pregnenolone in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.

Other Issues Caused by EBV

  • EBV increases risk for some cancers
  • EBV causes serotonin disturbances [6]
  • EBV affects methylation genes [7]
  • EBV may also cause blood-brain barrier issues [8]

Causes of EBV Reactivation

  • Emotional disturbances [9]
  • Psychological stress [5]
  • Cortisol/glucocorticoids [10]
  • Sleep deprivation – EBV DNA level increased significantly at both stress intervals [11]
  • Spaceflight [12]
  • Resistant starch/HDAC inhibitors – Helps kill the cancer cells, but induces EBV activation, but maybe only in the cancer cells [13]
  • Parthenolide – Also helps kill the cancer cells; another EBV activator, but maybe only in the cancer cells [14]

In a lot of my clients, I hear that their issues started after a highly stressful period. Reactivation of EBV could potentially play some role in the negative health effects of stress.

Top Supplements to Increase CD8+ T Cells

  • Resistant starch – The function of exhausted CD8 T cells in chronic viral infection was restored upon treatment with butyrate. This leads to higher numbers of CD8 T cells and mimics the effect of the pro-inflammatory cytokines IL-12 and IFN-α. This also increases CD8 T cell activation and memory [15]
  • Astragalus [16]
  • Andrographis – Increased in CD4+ (40 – 61%), CD8+ (23 – 31%), and CD56 (2 – 3%), with as little as 0.1μM
  • Gynostemma [17]
  • Schisandra – Prevents CD8+ decline from radiation [18]
  • NAC [19]
  • Ashwagandha [20]
  • Thymus glandular
  • Spleen glandular
  • Massage therapy [21]
  • Aldosterone (hormone)
  • ADA (enzyme) [22, 23]

Natural Killer Cells, Their Activity, EBV, and Autoimmunity

Many studies have reported decreased Natural Killer (NK) cell numbers or impairment of NK cell cytotoxicity in the peripheral blood of patients with autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s syndrome, systemic sclerosis, type I diabetes mellitus (T1DM), autoimmune thyroid disease (AIT), psoriasis, juvenile dermatomyositis, and systemic-onset juvenile idiopathic arthritis (JIA) [24, 25].

NK cells combat viral infections, release interferon gamma, kill activate T cells, and dampen the immune system in some ways [24].

Indeed, NK cells are used to treat certain autoimmune diseases [26].

So, low NK cells can cause autoimmunity in some ways. But it’s not so simple.

You can also interpret low natural killer cells in peripheral blood in another way. Several studies show an accumulation of NK cells in affected tissues of autoimmune patients. NK cells accrue in the pancreatic tissue of type 1 diabetics, the hair follicle of patients with alopecia areata, the muscle of children with juvenile dermatomyositis, the skin lesions of psoriatic patients, and the synovium of arthritis patients. Therefore, decreased NK cells in the peripheral blood with autoimmune disorders may result from them being shunted to diseased tissue [24].

NK cells may be directly involved in these diseases through their potential to attack our own tissue, or by their interaction (stimulation) with dendritic cells, macrophages, or T lymphocytes, thereby inducing excessive inflammation [26].

But, if you look at the big picture, it seems like NK cells and their function (cytotoxicity) do more to help prevent autoimmune disease, as a whole. However, the specific autoimmune disease and the environment of the person (what the rest of their immune system is like) probably plays a large role.

Bottom line: From my reading, NK cells seem like they can prevent autoimmune disease overall, but in some ways, they can contribute to it.

Inhibiting EBV Reactivation and Suppressing the Th1 System

Supplements that increase your Th1 system will indirectly prevent EBV reactivation by increasing interferon-gamma.

This list is a group of supplements that inhibit Th1 but also prevent its reactivation. I plan on creating a list of EBV inhibitors that also increase Th1 cells.

To prevent EBV reactivation you want to take Th1 supplements instead.

Methods for suppressing the Th1 system are located here.

In a cell study, sulforaphane inhibited reactivation [59].

There are probably many others, but these were the only ones that I could find sources for.

How Viruses Infect Cells

Irregular EBV Antibodies?

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