Epstein-Barr virus

Epstein-Barr virus (EBV) is part of the family of human herpes viruses. Infectious mononucleosis (IM) is the most common disease manifestation of this virus which, once established in the host, can never be completely eradicated. Very little can be done to treat EBV; most methods can only alleviate resultant symptoms. Sleep and rest—complete bedrest in severe cases—is still the best medicine for sufferers of this virus.

In addition to infectious mononucleosis, EBV has also been identified in association with—although not necessarily believed to cause—as many as 50 different illnesses and diseases, including chronic fatigue syndrome , rheumatoid arthritis , arthralgia (joint pain without inflammation ), and myalgia (muscle pain). While studying aplastic anemia (failure of bone marrow to produce sufficient red blood cells), researchers identified EBV in bone marrow cells of some patients, suggesting the virus may be one causative agent in the disease. Also, several types of cancer can be linked to presence of EBV, particularly in those with suppressed immune systems, for example, suffering from AIDS or having recently undergone kidney or liver transplantation. The diseases include hairy cell leukemia , Hodgkin's and non-Hodgkin lymphoma, Burkitt's lymphoma (cancer of the lymphatic system endemic to populations in Africa ), and nasopharyngeal carcinoma (cancers of the nose, throat, and thymus gland, particularly prevalent in East Asia ). Very recently, EBV has been associated with malignant smooth-muscle tissue tumors in immunocompromised children. Such tumors were found in several children with AIDS and some who had received liver transplants. Conversely, it appears that immunosuppressed adults show no elevated rates of these tumors.

Discovery, disease, and research

EBV was first discovered in 1964 by three researchers—Epstein, Achong, and Barr—while studying a form of cancer prevalent in Africa called Burkitt's lymphoma. Later, its role in IM was identified. A surge of interest in the virus has now determined that up to 95% of all adults have been infected with EBV at some stage of their lives. In seriously immunocompromised individuals and those with inherited immune system deficiencies, the virus can become chronic, resulting in "chronic Epstein-Barr virus" which is extremely serious and can be fatal.

Age and the health of the immune system play important roles in EBV-related illnesses. Infectious mononucleosis is the most common illness resulting from primary EBV infection . In young children, it often takes on mild flu-like symptoms that improve with time, or the symptoms are so mild they go unnoticed. However, ill or older people, IM can become a debilitating infection, and complications can affect almost every organ of the body, including possible rupture of the spleen. In fewer than 1% of IM cases, neurologic complications develop, and the patient can develop encephalitis , meningitis , Guillian-Barre syndrome, or other serious conditions. Very rarely, IM causes complications like aplastic anemia, thrombocytopenia (reduced numbers of platelets, the clotting factor in blood, resulting in bleeding), and granulocytopenia (severe reduction in white cells in the blood allowing the potential for "superinfection"). More commonly, however, IM causes persistent fevers; swollen and tender lymph glands in the neck, groin, and armpits; sore throat and even severe tonsillitis ; and sometimes a rash. Because the sore throat is so prominent, and because it may in fact become secondarily infected with strep, some patients are treated with ampicillin. Almost all of these individuals will break out in a rash which is often mistaken for evidence of a penicillin allergy . IM is almost always accompanied by fatigue and general malaise which can be quite severe initially, but bouts of which become less severe and prolonged over several weeks or months. Inflammation of the spleen and liver are also common in IM. The spleen in particular may grow very large, and may rupture spontaneously in about 0.5% of patients.

EBV is also implicated in another immune system-related illness called chronic fatigue syndrome (CFS). In several communities throughout the world, several epidemic-type outbreaks of what became known as CFS, including one in Lake Tahoe in 1985, baffled the medical community. There have been many conflicting theories in the ongoing search for the role of EBV in CFS. Initially, EBV was thought to be the causative factor; however, following intense studies performed during an outbreak of CFS in New York in 1985, it was determined that not everyone suffering from CFS developed antibodies to EBV. In cases where several children in one family all showed the same symptoms, only thee out of four showed infection by EBV. Further studies revealed that about one-third of the individuals affected by CFS had experienced primary infection with EBV years earlier and were once again fighting the virus. This syndrome became known as "active chronic EBV infection." In the other two-thirds of CFS sufferers, EBV levels were no different to those shown by the general population. It therefore seemed inaccurate to conclude EBV was the causative agent in CFS. Because some CFS patients experience reactivation of latent EBV, while in others EBV becomes active for the first time, it is possible that the effect of CFS on the immune system allows activation and reactivation of EBV. One theory about the interrelatedness of EBV and CFS is that, rather than causing CFS, EBV may, instead, trigger it.

Origin and development

EBV is restricted to a very few cells in the host. Initially, the infection begins with its occupation and replication in the thin layer of tissue lining the mouth, throat, and cervix, which allow viral replication. The virus then invades the B cells, which do not facilitate the virus's replication but do permit its occupation. Infected B cells may lie dormant for long periods or start rapidly producing new cells. Once activated in this way, the B cells often produce antibodies against the virus residing in them. EBV is controlled and contained by killer cells and suppressor cells known as CD4+ T lymphocytes in the immune system. Later, certain cytotoxic (destructive) CD8+ T lymphocytes with specific action against EBV also come into play. These cells normally defend the host against the spread of EBV for the life of the host.

A healthy body usually provides effective immunity to EBV in the form of several different antibodies, but when this natural defense mechanism is weakened by factors that suppress its normal functioning—factors such as AIDS, organ transplantation, bone marrow failure, chemotherapy and other drugs used to treat malignancies, or even extended periods of lack of sleep and overexertion—EBV escape from their homes in the B cells, disseminate to other bodily tissue, and manifest in disease.

Diagnostic blood tests cannot detect the virus itself. Infection is determined by testing for the antibodies produced by the immune system to fight the virus. The level of a particular antibody—the heterophile antibody—in the blood stream is a good indicator of the intensity and stage of EBV infection. Even though EBV proliferates in the mouth and throat, cultures taken from that area to determine infection are time-consuming, cumbersome, and usually not accurate.

Treatment is primarily supportive; encouraging rest and recuperation. When spleen enlargement is present, activities may need to be restricted to avoid the complication of splenic rupture. Antibiotics should be used only to treat documented bacterial infections which complicate the course of IM. Anti-viral medications do not seem to be helpful. Steroids should only be given in the rare instance of such complications as hemolytic anemia, severely swollen tonsils which are causing airway obstruction, or platelet destruction.

Disease transmission and prevention

Spread of the virus from one person to another requires close contact. Because of viral proliferation and replication in the lining of the mouth, infectious mononucleosis is often dubbed "the kissing disease." Also, because it inhabits cervical cells, researchers now suspect EBV may be sexually transmitted. Rarely is EBV transmitted via blood transfusion.

EBV is one of the latent viruses, which means it may be present in the body, lying dormant often for many years and manifesting no symptoms of disease. The percentage of shedding (transmission) of the virus from the mouth is highest in people with active IM or who have become immunocompromised for other reasons. A person with active IM can prevent transmission of the disease by avoiding direct contact—such as kissing—with uninfected people. However, shedding has been found to occur in 15% of adults who test positive for antibodies but who show no other signs of infection, thus allowing the virus to be transmitted. Research efforts are directed at finding a suitable vaccine .

The prevalence of antibodies against EBV in the general population is high in developing countries and lower socioeconomic groups where individuals become exposed to the virus at a very young age. In developed countries, such as the United States, only 50% of the population shows traces of antibody by the age of five years, with an additional 12% in college-aged adolescents, half of whom will actually develop IM. This situation indicates that children and adolescents between the age of 10 to 20 years are highly susceptible to IM in developed countries, making it a significant health problem among young students and those in the military.

Resources

books

Bell, David S. The Doctor's Guide to Chronic Fatigue Syndrome: Understanding, Treating, and Living with CFIDS. Reading, MA: Addison-Wesley, 1993.

Flint, S.J., et al. Principles of Virology: Molecular Biology,Pathogenesis, and Control Washington: American Society for Microbiology, 1999.

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

periodicals

Liebowitz, David. "Epstein-Barr Virus—An Old Dog With New Tricks." The New England Journal of Medicine 332, no. 1 (5 January 1995): 55-57.

Marie L. Thompson

KEY TERMS

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Antibody

—A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells.

Arthralgia

—Joint pain without inflammation.

B cell

—Immune system white blood cell that produces antibodies.

Immunosuppressed/immunocompromised

—Reduced ability of the immune system to fight disease and infection.

Myalgia

—Muscular aches and pain.

Nasopharyngeal

—Of the nose and throat.

T cells

—Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.