Epstein-Barr Virus' Ability To Form And Sustain Tumors, Clue Found By Researchers

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BlankEpstein-Barr Virus' Ability To Form And Sustain Tumors, Clue Found By

Researchers

07 Sep 2006

Researchers at the University of Wisconsin School of Medicine and Public Health

(SMPH) have found a viral target that opens the door for the development of

drugs to destroy tumors caused by Epstein-Barr virus (EBV).

The finding, published in the Sept. 4 Proceedings of the National Academy of

Sciences Online, identifies the activity of a critical segment of a viral

protein required to sustain EBV-related tumors. The researchers found that 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, an often-fatal malignancy affecting thousands of African children

annually. 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 SMPH researchers, based at the McArdle Laboratory for Cancer Research,

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 tumors.

" 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-tumor therapy for all EBV-positive tumors. "

In the current study, Sugden and his colleague of 20 years, Wolfgang

Hammerschmidt, now based at the German National Research Center for Environment

and Health, 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 RNA and then into

protein.

Mutating the unique segment of amino acids prevented EBNA-1 from transforming

resting B cells into proliferating cells.

Under normal conditions, a cellular protein binds this 25-amino acid segment of

EBNA-1, allowing transcription of viral and cellular genes regulated by EBNA-1

to occur. Hammerschmidt and Sugden are now trying to identify the cellular

protein.

" If we can identify this protein, it will be easier for us to develop assays to

screen for small molecules that will compete with the protein in binding to

EBNA-1, " Sugden says. " By preventing the cellular protein from binding with the

segment, EBNA-1 will not be able to carry out its function and the tumor cells

it sustains will die. "

The goal, which Sugden expects is achievable, is to end up with a drug that

kills only EBV-positive tumor cells and doesn't harm other tissues in the body.

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Contact: Dian Land

University of Wisconsin-Madison

Article URL: http://www.medicalnewstoday.com/medicalnews.php?newsid=51246