A tale of fevers, cancers and hijacking

It has infected 95% of humans in the developed world, can cause glandular fever and has been linked to the development of some cancers. Now scientists think that Epstein-Barr virus establishes it’s self by hijacking a protein that normally causes cell death.

Electron microscopic image of two Epstein Barr Virus virions (Credit Liza Gross)

Researchers based in the German National Research Centre for Environment and Health have investigated the way that the virus manipulates TRADD - a human protein that causes apoptosis - in order to establish itself in the host.

Epstein-Barr virus alters the way B lymphocytes behave, transforming them into cancerous cells that survive and divide more than they should. The team were surprised that TRADD was involved in transforming cells to do this, as in a healthy person it is important in doing just the opposite: it causes apoptosis - organised cell death.

Lead researcher, Dr. Arnd Kieser, said: “It is amazing to learn which sophisticated molecular means this human tumor virus has developed to take control of the communication system of its host cell.”

The team studied the way that TRADD interacts with LMP1, a protein produced by the virus that is essential for cell transformation. They genetically altered cells so that they wouldn’t produce any TRADD and found that these cells didn’t respond to the transformation signals sent by the LMP1 protein, showing that TRADD is necessary for this change.

When TRADD is bound to LMP1, it is unable to interact with the molecules that it normally would, and so cannot cause cell death.

They then took the unique TRADD binding site that they had identified on the viral protein and used it to replace the TRADD binding site on the host cellular protein that mediates cell death. This was enough to convert the cellular protein into a non-apoptotic receptor and thus to stop TRADD from inducing apoptosis. This was further evidence that they correctly identified the mechanism that the viral protein uses to transform B lymphocytes.

“The unique interaction of LMP1 with TRADD could serve as a target structure for drug development against EBV-induced cancers.” Dr. Arnd Kieser