Protein may be culprit for kissing disease

October 7, 1999
Web posted at: 3:48 PM EDT (1948 GMT)

By Christine Cosgrove

(WebMD) -- Japanese and American researchers have discovered how the Epstein-Barr virus takes over certain immune system cells in order to promote its own replication and spread throughout the body, according to a study in this week's issue of the journal Science.

The virus, best known for causing infectious mononucleosis, or "kissing disease," has also been implicated in a number of cancers, particularly among people who have undergone organ transplants. In addition, the virus has been linked to several specific cancers, including nose and throat cancers, stomach cancers and lymphomas: cancers in the lymphatic system including the spleen, tonsils and thymus.

The findings shed light on how the virus infects B cells, which play a major role in the body's immune system, the researchers say. The study results also help to explain how a low level of these virus-infected B cells manages to stay alive in the body even when the immune system is functioning perfectly well.

Behind the virus's newly discovered ability is a protein (LMP1) that is produced by the virus and mimics CD40, an important molecule found in the virus-fighting arsenal of another immune cell, said study co-author Nancy Raab-Traub, professor of microbiology and immunology at the University of North Carolina at Chapel Hill's Lineberger Comprehensive Cancer Center.

The malignancy process

Working with colleagues from Osaka University in Japan, Raab-Traub and her associates made their discovery by mating mice missing the CD40 molecule with mice carrying the LMP1. Mice born from those pairings showed researchers how the virus subverts the immune system's communication process and makes the cell more hospitable for itself.

"What this research shows is that this virus can take over a pathway that regulates how [certain immune cells] fundamentally behave and use that pathway for its own purposes," said Elliott Kieff, professor of medicine and microbiology and molecular genetics at Harvard University.

"This virus is fundamentally altering the growth of the cells and can cause malignancies of various kinds," he added. "But it's finely balanced in how it does this, so it's usually recognized in the normal host and kept at bay."

In individuals with compromised immune systems, however, the virus appears to promote the development of lymphoma. Among organ transplant patients, whose immune systems are suppressed, the risk of lymphoma is quite high, said Kieff.

Just how the virus is involved in other cancers is not completely clear, said Raab-Traub. But it's likely that certain environmental factors can prompt a latent virus to reactivate.

Studying the water

For example, scientists have found that in Southern China, where most people have been infected with the Epstein-Barr virus, there is an extraordinarily high rate of a certain type of nose and throat cancer, which is rare in other parts of the world.

In addition, the drinking water in this part of China appears to reactivate the virus and aid its replication, said Raab-Traub.

The culprit in the water appears to be the leaves of euphorbia trees, which line many canals in the area, she said. In laboratories, a compound isolated from euphorbia trees is used to make the Epstein-Barr virus replicate when larger quantities of the virus are needed for research.

Virologist Christopher Beisel, program director at the National Institute of Allergy and Infectious Diseases, said all of this new information could conceivably help in finding ways to lessen the severity of mononucleosis symptoms.

When young children pick up the virus, their symptoms go almost unnoticed. But when teen-agers and young adults contract the virus, they develop infectious mononucleosis, which comes with a host of unpleasant symptoms such as fatigue, weakness and loss of appetite.

Beisel added, however, that it would be "premature" to speculate that the new research points to a specific treatment or prevention for cancer.

According to the institute, 50 out of 100,000 Americans develop mononucleosis symptoms every year.

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RELATED SITES:

University of North Carolina at Chapel Hill
Infectious mononucleosis
National Center for Infectious Diseases
National Institute of Allergy and Infectious Diseases

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