Epstein Barr Virus (EBV) and Lymphoma

Epstein-Barr virus, artistic rendering..

A number of germs -- including bacteria, viruses and parasites -- are associated with lymphoma.

The Epstein-Barr virus (EBV) is a type of virus that infects many people around the world. In fact, over 90 percent of the entire human population eventually becomes infected with EBV, and the virus persists for a lifetime, though its presence may be insignificant for many.

Most people recognize infectious mononucleosis, or mono, as the kissing disease that a teen, adolescent or college student might contract.

This is what may happen when an adolescent is infected, but elsewhere and throughout the world, infection with this virus usually occurs earlier, in childhood, perhaps as a throat infection. Most EBV infections in children are asymptomatic or cause non-specific symptoms, whereas first infection during adolescence can result in infectious mononucleosis in 50 percent of patients.

What makes EBV different from the point of view of lymphoma is that it has a unique set of genes that causes a growth activation of the cells that it infects. EBV mainly infects B-cells (a type of white blood cell). While most of the time the infection causes little damage, sometimes the growth activating genes in B-cells that may be associated with cancers in certain people. Therefore, EBV is considered a risk factor for certain kinds of lymphoma.

EBV and Lymphoma Cancers

The most common cancers caused by EBV are lymphomas.

The two main categories of lymphoma are Hodgkin’s and non-Hodgkin’s lymphoma, and EBV has been associated with subtypes within each of these two main categories. In addition to lymphomas, some cancers of the nasopharynx -- the upper part of the throat behind the nose – may be linked to EBV.

Post-Transplant Lymphoma and AIDS-Associated Lymphoma

EBV is strongly related to developing lymphoma after organ transplants. After any sort of organ transplantation, those receiving the transplant have to be given drugs that prevent an immune response to foreign material. This allows the transplanted organ to avoid immune rejection by the recipient, but these drugs unfortunately can weaken the immune system and make the body susceptible to different viral infections, including EBV. During AIDS too, there is a loss of immune control over viral infections in the body. Under certain circumstances, viruses like EBV can cause abnormal growth of infected B-cells and help turn them into lymphomas.

Burkitt's Lymphoma and Malaria

Burkitt lymphoma, or BL is the most common non-Hodgkin lymphoma in children and adolescents around the world. In many parts of Africa, EBV is strongly linked to Burkitt’s lymphoma. In particular, having an early EBV infection is linked with the development of BL. EBV causes specific genetic changes that help turn B-cells into cancer.

Repeated malarial infection also helps EBV to cause lymphomas.

The disease was named after Dr. Denis Burkitt, an Irish missionary-surgeon who worked in Africa. Burkitt and colleagues discovered BL in 1957, where cases were clustered in regions where malaria was endemic -- the so-called lymphoma belt. However, malaria is a parasite that infects the red blood cells, not the white blood cells of lymphoma, and so the exact mechanism had been a mystery for 50 years.

In the summer of 2015, however, some light was shed on the subject, albeit in animal studies. Working with mice, researchers at Rockefeller University led by Michel Nussenzweig found that the same enzyme that helps make antibodies to fight malaria also causes DNA damage that can lead to Burkitt’s lymphoma. The research was published August 2015 in the journal "Cell."

Hodgkin's Lymphoma

Hodgkin's lymphoma, or HL, is another type of lymphoma that is linked to EBV. In western countries, nearly 40 percent of individuals with HL are also infected with EBV. The infection rate may be even higher in many other parts of the world. The exact mechanism by which EBV may cause Hodgkin's lymphoma is not well understood, but it is becoming very evident that EBV has an important role to play in the development of this lymphoma. Though it may be associated with different types of Hodgkin’s disease, the most common is mixed cellularity, classic Hodgkin’s lymphoma. HL in the older age groups and in children, especially boys under 10 years, has been shown to be more likely to be EBV-associated than HL in young adults.

EBV-positive Diffuse Large B-cell Lymphoma of the Elderly

Though diffuse large B-cell lymphoma (DLBCL) has been recognized for some time, EBV-positive DLBCL of the elderly was first described in 2003, and is listed provisionally in the 2008 World Health Organization classification system – which defines it as “an EBV-positive monoclonal large B-cell proliferation that occurs in patients >50 years of age and in whom there is no known immunodeficiency or history of lymphoma.” This malignancy is more common in Asia but also occurs in North America and Europe at a low frequency.

Sources:

Brady G, MacArthur GJ, Farrell PJ. Epstein–Barr virus and Burkitt lymphoma. Journal of Clinical Pathology. 2007;60(12):1397-1402.

Kapatai G, Murray P. Contribution of the Epstein–Barr virus to the molecular pathogenesis of Hodgkin lymphoma. Journal of Clinical Pathology. 2007;60(12):1342-1349.

Ok CY, Papathomas TG, Medeiros LJ, Young KH. EBV-positive diffuse large B-cell lymphoma of the elderly. Blood. 2013;122(3):328-340.

The Rockefeller University. Science News. New research helps explain why a deadly blood cancer often affects children with malaria. Accessed April 2016.

 

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