CHAPEL HILL - Scientists at the University of North Carolina at Chapel Hill, working with colleagues in Japan, have proven that a protein called latent membrane protein 1 in Epstein-Barr virus causes a form of cancer known as B cell lymphoma in mice.
The work is important, the scientists say, because it shows the protein's central role in Epstein-Barr virus' ability to change normal cells into cancerous ones. That virus already is known to cause infectious mononucleosis in humans and has been associated with such malignancies as Burkett's lymphoma, Hodgkin's lymphoma and nose and throat cancer. It is especially hazardous to AIDS patients and other patients whose immune systems have weakened.
"We have shown for the first time that Epstein-Barr virus clearly can cause cancer," said Dr. Nancy Raab-Traub, professor of microbiology at the UNC-CH School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. "Now we can go after the specific protein that is responsible and perhaps one day stop that protein function and prevent the cancer from growing."
The first report on the continuing research appeared in the Proceedings of the National Academy of Sciences last year, and a second describing additional findings is being published in Friday's (Oct. 8) issue of the journal Science.
In the Proceedings paper, Raab-Traub and her colleagues described breeding three different lines of laboratory mice into which the latent membrane protein 1 (LMP1) from Epstein-Barr virus was genetically incorporated. Lymphoma developed in all three strains of mice, which are known as transgenic mice, and had affected 42 percent of the animals within 18 months.
Investigators detected the protein in high concentrations in cancerous tissue, but only in trace amounts in normal lymph system tissues.
"This work demonstrated that LMP1 alone -- without expression of other Epstein-Barr virus genes -- causes cancer in animals and is a major contributing factor to development of Epstein-Barr virus lymphomas," Raab-Traub said.
The new report describes experiments in which those mice were crossed with other mice in which a molecule called CD40 had been knocked out, or incapacitated, she said. CD40 is involved in maturation of B cells, which are white blood cells that make immunoglobulin antibodies. Humans bearing a mutation preventing CD40 function cannot produce effective antibodies.
Because CD40 and LMP1 have been shown to interact with the same cellular proteins, the researchers crossed the mice to learn whether LMP1 could partially substitute for CD40 in the immune-deficient mice. That's exactly what happened.
"The mice could now make immunoglobulins in a process called class switching," Raab-Traub said. "But LMP1 seemed to specifically impair the ability of mice that had CD40 to make something called a germinal center, where B cells mature.
"These experiments tell us something important about how the virus manages to persist in the body and where it is." A National Cancer Institute grant to Raab-Traub supports the research.
Note: Raab-Traub can be reached at (919) 966-1701.
Lineberger Cancer Center Contact: Dianne Shaw, 966-5905.
News Services Contact: David Williamson, 962-8596
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