Biologists shed light on cell reactions to Epstein-Barr Virus

Discoveries made by Duke researchers may help to explain how cells respond after infected by Epstein-Barr Virus (EBV), a virus that causes cancer.

The recent study, which appeared in Proceedings of the National Academy of Sciences, found that if supplies of nucleotides and other cell-building materials run low, a large population of EBV-infected B-cells stop dividing after they hit their first period of rapid growth. The stoppage of cell division could freeze the advance of the EBV virus—preventing the transformation of B-cells into cells that can reproduce indefinitely and potentially cause cancer in immunosuppressed individuals. B-cells are responsible for producing antibodies.

The study’s lead author was Micah Luftig, associate professor of molecular genetics and microbiology in the Duke School of Medicine and deputy director of Duke’s Center for Virology.

“The overall finding here is that when cells hit the first period of proliferation after infected by EBV, there is a strain put on the cells’ metabolism and cells will undergo autophagy, which is basically cells eating themselves to gain enough nutrients to promote cell survival,” said Amy Hafez, a fourth- year graduate student in the Department of Molecular Genetics and Microbiology, who was also an author of the study. “However, cells ultimately arrest if not enough nutrients are available.”

Hafez explained that the research focused on the EBV virus, which is the first virus shown to cause cancer in humans. It is found in more than 90 percent of adults worldwide, but a strong immune system usually stops the virus from making much headway.

Many of the cancers, such as lymphoma, that are linked to EBV are found in immunocompromised patients—including those with HIV/AIDS or malaria—whose ability to fight off disease has been weakened.

When EBV infects B-cells, it causes the cells to grow and divide abnormally fast for a short period of time, Luftig said. This causes the cell to undergo metabolic stress and change that helps to keep up with the rapid proliferation.

“What we want to do is to get more detailed molecular understanding of what the cells do following the proliferation,” he said.

Luftig explained that all of the studies were done with human B-cells and human blood, which researchers acquired from normal donors. Although this method makes the findings more physiologically relevant, he said primary cells are more difficult to work with, which necessitates constant shifting to maintain fresh samples.

This study provides a better understanding of pathways to prevent cancer and sheds light on potential drug targets that may suppress EBV-associated cancer development in immune-deficient patients, noted Hafez.

“In the study, we used the drug which is actually used for certain cancer. It can inhibit a pathway that is important for cell growth, and also affects some metabolisms,” Luftig said. “So this drug inhibits EBV infected B-cells proliferation. So this would be a model for cancer treatment.”

The group’s future research will focus on the early stage when the cell slows down from proliferation to investigate what changes are happening.

“One of the interesting findings that we made since we published the study is that we confirmed that we can overcome the growth by increasing nucleotides of DNA,” Luftig said.