In the early 1960s, a young researcher and his assistant not only discovered the virus that would bear their names - Epstein-Barr - but made the revolutionary connection between the "bug" and a rare form of fast-growing lymphoma in African children. Today, most Americans have heard of Epstein-Barr because it causes fatigue, sore throat, fever and swollen glands, hallmarks of the violent immune response seen in mononucleosis. But to many patients, researchers, and physicians, Epstein-Barr means more than missing a few weeks of school or work; the virus is linked to cancers of the nose and upper throat, common in people of southern Chinese descent, as well as Hodgkin's disease, and other lymphomas.
Elliott Kieff, MD; PhD, chief of the Division of Infectious Disease at BWH, has been studying the Epstein-Barr virus for more that 30 years. Prevalent throughout the world, EBV is transmissible through saliva and infects 95 percent of Americans, but most will never know it because the virus can lie dormant for a lifetime.
" There are other viruses that cause cancer," Kieff says, citing, for example, human papilloma virus, which is associated with cervical cancer. "But Epstein-Barr is the only one we know of that takes a human cell and routinely makes it grow in a potentially malignant way."
Epstein-Barr has been definitively linked to cancers in people who are genetically predisposed to the cellular changes it can induce, as well as to cancers in individuals with compromised immune systems, including African children with malaria, HIV-infected individuals, and transplant recipients. "The virus is a major problem when it's transmitted through a transplant," Kieff notes. "Since these patients are on immunosuppressive drugs, they usually can't fend off the growth of virus-infected cells."
In 1982, Kieff and his research team launched an effort to develop an EBV vaccine. Tests of its safety and efficacy began two years ago in several hundred volunteers, including a small number of patients. "Getting a drug or vaccine on the market can be difficult," Kieff says. "Lots of times you get it into clinical studies, only to find that it's not doing exactly what you thought it would do. There is not perfect knowledge here."
Perhaps, but new knowledge is certainly offering hope: Kieff's team recently learned how EBV proteins alter human cells. "We've identified the steps in the process," Kieff says. "Knowing those steps gives us the power to interfere with them. We hope to identify chemicals that can do this."
Compounds that halt Epstein-Barr's cellular changes could be available in as little as two years for testing in animal models now being developed by Frederick Wang, MD, medical director of the BWH Clinical Virology Laboratory. Kieff again cautions that progress in research in unpredictable, but adds, "We've had enough success so far to keep us enthusiastic."