The Secret Life of the Epstein-Barr Virus

Epstein-Barr virus is the most common viral infection in humans. It can lay dormant for years and cause crippling long-lasting fatigue. But most people never know that they have been infected.

When fatigue stretches beyond the typical exhaustion posed by everyday life, it can be a conundrum for both sufferers and doctors. After a slew of likely contenders such as heart disease, anemia, thyroid disease, depression or a sleep disorder are ruled out, getting to the source of fatigue gets murky.

Among the many next-tier suspects is the Epstein-Barr virus (EBV). EBV belongs to the family of herpes viruses including those that cause cold sores, genital herpes, chickenpox and shingles. Infection with EBV is virtually inescapable; in the US, 95% of all adults will be infected by age 40, and 50% of all children by age 5. Many people don't realize they have been infected because they never feel sick. Once infected however, you harbor the virus for good. There is growing concern about the aftereffects of an EBV infection; a number of chronic diseases, including some types of cancers, have been linked to this infection.


The Epstein-Barr Virus M.O.

Unlike bacteria, which multiply comfortably on their own given the right environment, viruses need to insert themselves into a host's cells in order to persevere. Once a virus has taken a human cell hostage, it continues to conquer cell after cell.

For the most part, a healthy immune system can derail these viral interlopers so they don't do too much damage. The virus is detected, a customized antibody is made and an all out attack is mounted by killer cells. But like other herpes viruses, EBV is quite clever and can evade an all out antibody strike. It can stay in suspended animation for the rest of a person's life. lying dormant for months or years. There are no good treatments, no cures and no vaccines to prevent the spectrum of diseases (testing of a EBV vaccine is currently underway).

The EBV Infection Spectrum

EBV has a particular affinity for the cells that line the mouth and throat. Once the virus inserts itself into to a specialized immune lymphocyte (B cell), it hijacks the DNA to take control of the cell forever. When cells of the mouth and throat naturally slough off, EBV is shed into saliva. Anyone coming in contact with the virus-laden mucous becomes infected.

Children are susceptible as soon as the mother's protective immunity wanes. When very young children are exposed they may experience mild symptoms or none at all. The symptoms are not unique and mimic many run-of-the-mill childhood infections that also cause sore throat, fever and swollen glands.

Infections that occur later can produce a wide range of symptoms if any at all. It may take between 30-50 days for symptoms to appear.


Infectious Mononucleosis

When teenagers are exposed, about half will get mononucleosis (mono) or 'kissing disease." A few weeks after contact with EBV, monocyctes, a certain type of white blood cell, grow unchecked, filling up in lymph tissue. Teens can be laid up for weeks, sometimes months, before the fatigue lifts and they begin to feel normal again.

Symptoms of mononucleosis include

  • Fever
  • Extreme fatigue
  • Swollen glands
  • Sore throat
  • Painful swallowing
  • Enlarged lymph nodes in neck and under arms
  • Enlarged spleen
  • Enlarged liver
  • Anemia
  • Red spots on the roof of the mouth
  • Eye swelling
  • Rash

Chronic Active EBV Infection

Very rarely an active EBV illness persists beyond 6 months. The fatigue is unrelenting and often confused with chronic fatigue syndrome, which thus far has no solid association with EBV. Doctors can identify an active EBV infection because the levels of EBV antibody circulating in the blood remain very high. They can also detect the virus itself when organ tissue is sampled and tested for EBV DNA. Chronic infection can affect the lungs, liver, bone marrow and eyes.


EBVs relationship to cancer actually began back when the virus was first discovered. In the early 60s, Drs. Epstein and Barr were examining tissue from a patient with Burkitt's lymphoma when they discovered the virus. Since then the EBV stamp can be found in other cancers including cancer of the nasopharynx (cavity behind the mouth), Hodgkin's disease, non-Hodgkin's lymphoma, and oral hairy leukoplakia in patients with the acquired immunodeficiency syndrome (AIDS). Since not everyone infected with EBV gets cancer, other environmental or genetic factors must increase susceptibility for cancer.

Multiple Sclerosis

One of the most compelling findings of late is EBV's role in the autoimmune disease multiple sclerosis (MS). People with MS have a faulty immune response that causes immune cells to mistakenly attack the protective insulation (myelin) surrounding nerve fibers. When the myelin sheath is stripped it interferes with the transmission of nerve messages throughout the body and brain causing a wide range of neurological problems depending on where the damage occurs.

There are a few things that link the MS to EBV infections.

  • Nearly everyone with MS tests positive for EBV
  • People clear of the virus don't get the disease
  • High levels of EBV antibodies precede MS symptoms and flare-ups
  • Infectious mononucleosis doubles the risk for MS

EBV infection is probably not the sole cause for this complex disease and it is likely that outside factors trigger MS. One new piece of the puzzle has recently emerged. Vitamin D , abundant in oily fish, fortified foods and manufactured by the body when the skin is exposed to the sun, might be important for the healthy immune-fighting cells. Low vitamin D may cause immune pathways to go haywire, causing misguided immune cells to see the myelin sheath as foreign. The full picture is not yet in focus but increasing the amount of vitamin D through diet or dietary supplements may protect against MS.


Tests for EBV

The only way to know for sure if an active EBV infection is the cause of fatigue is to get tested. If you have been exposed to the virus your immune system will make antibodies that the test will measure; tests measure the concentration of 6 types of EBV antibodies and the level can indicate if the infection is current or a past infection. A rising or high antibody level after at least 4 weeks of illness suggests an active infection. A positive reaction to the Monospot test indicates active mononucleosis.

There are also molecular tests that measure EBV DNA, which can help diagnose EBV-related cancers.

Tracing the Cause of Fatigue

To get to the source of fatigue that lasts longer than a few months you almost have to be a sorcerer. Doctors will use a systematic approach to making a diagnosis focusing on the most likely causes first. Distinguishing between sleepiness and fatigue is the first step.

Here are some questions that need to be answered to help you and your doctor narrow down the cause of fatigue.

  • Is your sleep disturbed (sleeping too little, too much) or not restorative?
  • Do you have any other physical symptoms such as pain, fever, muscle weakness or swelling?
  • Does the fatigue fluctuate throughout the day?
  • Does rest help?
  • Are you getting enough exercise?
  • Are you regularly eating a nutritious diet?
  • Are you overweight?
  • Have you had a blood test to check for anemia, diabetes, hepatitis or thyroid disease?
  • Have you been bitten by any insects?
  • Are you low in vitamin D?
  • Are you experiencing an episode of depression or anxiety?
  • Could you be pregnant?
  • Could you be experiencing an over-the-counter or prescription medication side effect?
  • Have you had age-appropriate cancer screening tests?
  • Do you have any type of heart disease?
  • Are you abusing alcohol, prescription medications or recreational drugs?