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Waking a sleeping virus

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A detailed structural picture of a molecule that plays a key role in activating the Epstein Barr Virus in human cells has now been obtained by researchers at the European Molecular Biology Laboratory (EMBL) and the Institut de Virologie Moléculaire et Structurale (IVMS), associated with the Université Joseph Fourier and the CNRS, in Grenoble.

Like Sleeping Beauty, the Epstein Barr Virus (EBV) slumbers in the cells of 90 per cent of the world's population, waiting to be awakened ?but it's no beauty. The study, which appears in this week's issue of the journal Molecular Cell, also reveals a potential weak point that could be targeted by antiviral drugs.

The molecule is a protein called ZEBRA, which the virus brings along as it infects human cells. ZEBRA is essential to switching the virus from its latent to its active state. "During an infection, EBV inserts its own DNA into the nucleus of human cells. This information contains the codes for about 100 genes," says Christoph Müller, head of an EMBL research lab in Grenoble. "Less than 10 genes are sufficient for the virus during its latent state, whereas all others are necessary to produce new viruses and to infect new host cells. Those have to be switched on, and ZEBRA functions as the switch which turns the cell into a factory to manufacture thousands of copies of the virus."

One result is the disease infectious mononucleosis ?called the "kissing disease" because EBV is transmitted in saliva ?whose symptoms resemble that of a cold. But in rare cases activation of the virus also leads to EBV associated cancers, especially in people with immune deficiencies.

Researchers have focused on ZEBRA because of its ability to activate so many genes. It does so by recognizing specific strings of chemical "letters" in the DNA, docking onto them and allowing the information to be read and transformed into ra
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Source:European Molecular Biology Laboratory


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