Breaking the Virus Life Cycle

A viral protein might take the
terror out of Epstein-Barr virus
© NCI Visuals Online

They have identified the activity of a critical segment of a viral protein required to sustain Epstein-Barr virus (EBV)-related tumours - when they blocked this activity, the virus life cycle was broken.

Often linked to infectious mononucleosis, EBV also causes cancers that kill 100,000 people around the world each year. The virus, which infects the immune system's B cells and causes them to grow, is directly responsible for Burkitt's lymphoma. It is also causally associated with at least four other kinds of human cancers, including Hodgkin's lymphomas, lymphomas in AIDS patients and organ transplant recipients as well as nasopharyngeal carcinomas.

The University of Wisconsin School of Medicine and Public Health (SMPH) researchers focused on a viral protein they had previously found to be necessary to keeping Burkitt's lymphoma cells alive and growing in culture. The protein, called Epstein-Barr nuclear antigen 1 (EBNA-1), is the only protein the virus makes in all EBV-positive tumours.

"We've been trying to identify specific functions of EBNA-1 that we could target therapeutically," says Bill Sugden, professor of oncology who has studied EBV for more than 30 years. "Our goal is to develop a successful anti-viral, anti-tumour therapy for all EBV-positive tumours."

In the current study the scientists designed genetic experiments to mutate various segments of the 640 amino acids that make up the EBNA-1 protein, which is one of about 100 proteins EBV encodes. They then infected human B cells with EBVs carrying various mutant EBNA-1s.

The analysis showed that one 25-amino acid segment within EBNA-1 was responsible for the regulation of viral gene transcription, the first step in the process by which a gene's coded information is converted first into Ribonucleic acid (RNA) and then into protein. Mutating the unique segment of amino acids prevented EBNA-1 from transforming resting B cells into proliferating cells.; Source: University of Wisconsin-Madison