21 February 2006

Sleeper Virus Waits to Trigger Cancer in 90% of Humans

Epstein Barr Virus, EBV, infects most humans during their childhood. For most, the symptoms are mild, like a passing cold. For some, the infection manifests as mononucleosis, with side effects that can range from hepatitis to splenic rupture to heart and CNS involvement. Like other herpes viruses, EBV sticks around after the initial infection, sleeping and waiting.

Sometimes the sleeping virus wakes up and causes cancer--Burkitt's lymphoma or nasopharyngeal carcinoma. Sometimes persons with vague immune disorders or fatigue syndromes reveal nothing more on laboratory tests than latent or chronic EBV infection.

Medical News Today has a newsrelease about the sleeping EBV and a possible weakness in the virus that might be exploited.

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 raw materials to make new viruses.

"A good strategy in fighting viruses is to block the activation of viral genes," says Patrice Morand, a physician at the University hospital and the IVMS. "The drugs we currently use against EBV work that way. The problem is that they only interrupt the late phase of the viral cycle. Since ZEBRA is essential to the first steps, waking the virus, blocking it would be much better."

The researchers utilised the tools of genomics and proteomics to find the target protein, and potential drug targets on its surface. Read the entire article for more details.
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