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Molecular Piracy Turns Protein Into Traitor

New Chemokine Holds Hope For HIV Treatment

An act of molecular piracy may put Glaxo Wellcome scientists on the track of drugs that would prevent HIV from entering human cells. Human herpes virus 8 (HHV-8) appears to have stolen a gene from the human host which codes for a chemokine. The virus then transformed it into a potent and broad-spectrum blocker of our chemokine system. Recent research has shown that two of the chemokine receptors blocked by the new molecule, CCR5 and CXCR4, are co-receptors essential for HIV infection of human cells.

This is the first naturally occurring chemokine antagonist. In humans, chemokines, also called chemoattractant cytokines, regulate the movement of white blood cells. However, in this case, the virus has modified the original human chemokine so that it binds to the chemokine receptor but does not stimulate the normal response. Instead, the resulting viral chemokine, vMIP-II, acts as an antagonist blocking the normal action of the receptor. Even more surprisingly, vMIP-II is able to block two distinct types of chemokine receptors, so called CC and CXC receptors. This is the first known molecule able to bind to both types of receptor.

The biological process the virus used to develop vMIP-II is not unlike the chemical process used by Glaxo Wellcome scientists to find new drugs. After lifting a human gene for a chemokine receptor agonist, the virus used genetics to perform a type of biological 'combinatorial chemistry'. This process can be used to produce a family of similar molecules. The virus then tested the related molecules against our own immunological defence mechanisms, making modifications until it found a molecule with the desired properties. In this particular case, the virus was hunting for a molecule that would prevent an inflammatory immune response that might clear the virus.

"The hope is that by understanding how the virus m
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Contact: Philip Connolly
pcg2355@ggr.co.uk
+44 181 966 8185
GlaxoSmithKlines
5-Sep-1997


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